{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T17:45:34Z","timestamp":1791395134966,"version":"4.3.3"},"reference-count":320,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T00:00:00Z","timestamp":1661990400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research AIRC","doi-asserted-by":"publisher","award":["MFAG 26004"],"award-info":[{"award-number":["MFAG 26004"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant melanoma represents the most fatal skin cancer due to its aggressive behavior and high metastatic potential. The introduction of BRAF\/MEK inhibitors and immune-checkpoint inhibitors (ICIs) in the clinic has dramatically improved patient survival over the last decade. However, many patients either display primary (i.e., innate) or develop secondary (i.e., acquired) resistance to systemic treatments. Therapeutic resistance relies on the rewiring of multiple processes, including cancer metabolism, epigenetics, gene expression, and interactions with the tumor microenvironment that are only partially understood. Therefore, reliable biomarkers of resistance or response, capable of facilitating the choice of the best treatment option for each patient, are currently missing. Recently, activation of nicotinamide adenine dinucleotide (NAD) metabolism and, in particular, of its rate-limiting enzyme nicotinamide phosphoribosyltransferase (NAMPT) have been identified as key drivers of targeted therapy resistance and melanoma progression. Another major player in this context is the mammalian target of rapamycin (mTOR) pathway, which plays key roles in the regulation of melanoma cell anabolic functions and energy metabolism at the switch between sensitivity and resistance to targeted therapy. In this review, we summarize known resistance mechanisms to ICIs and targeted therapy, focusing on metabolic adaptation as one main mechanism of drug resistance. In particular, we highlight the roles of NAD\/NAMPT and mTOR signaling axes in this context and overview data in support of their inhibition as a promising strategy to overcome treatment resistance.<\/jats:p>","DOI":"10.3390\/ijms23179985","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T21:27:17Z","timestamp":1662067637000},"page":"9985","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["NAD\/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8686-4106","authenticated-orcid":false,"given":"Alice","family":"Indini","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Department of Medicine and Surgery, Ospedale di Circolo e Fondazione Macchi, ASST dei Sette Laghi, 21100 Varese, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Fiorilla","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation, University of Eastern Piedmont, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6145-129X","authenticated-orcid":false,"given":"Luca","family":"Ponzone","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center \u201cGuido Tarone\u201d, University of Turin, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4439-9709","authenticated-orcid":false,"given":"Enzo","family":"Calautti","sequence":"additional","affiliation":[{"name":"Department of Molecular Biotechnology and Health Sciences, Molecular Biotechnology Center \u201cGuido Tarone\u201d, University of Turin, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5660-4175","authenticated-orcid":false,"given":"Valentina","family":"Audrito","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation, University of Eastern Piedmont, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/s41586-019-1730-1","article-title":"A view on drug resistance in cancer","volume":"575","author":"Vasan","year":"2019","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1016\/j.trecan.2019.02.003","article-title":"Polytherapy and Targeted Cancer Drug Resistance","volume":"5","author":"Chatterjee","year":"2019","journal-title":"Trends Cancer"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/nrc.2016.37","article-title":"From melanocytes to melanomas","volume":"16","author":"Shain","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"626129","DOI":"10.3389\/fonc.2020.626129","article-title":"Decoding Melanoma Development and Progression: Identification of Therapeutic Vulnerabilities","volume":"10","author":"Eddy","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1681","DOI":"10.1016\/j.cell.2015.05.044","article-title":"Genomic Classification of Cutaneous Melanoma","volume":"161","year":"2015","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1056\/NEJMoa1904059","article-title":"Five-Year Outcomes with Dabrafenib plus Trametinib in Metastatic Melanoma","volume":"381","author":"Robert","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/S1470-2045(18)30142-6","article-title":"Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): A multicentre, open-label, randomised phase 3 trial","volume":"19","author":"Dummer","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1056\/NEJMoa1504030","article-title":"Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma","volume":"373","author":"Larkin","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2521","DOI":"10.1056\/NEJMoa1503093","article-title":"Pembrolizumab versus Ipilimumab in Advanced Melanoma","volume":"372","author":"Robert","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1038\/nrclinonc.2017.43","article-title":"Targeted agents and immunotherapies: Optimizing outcomes in melanoma","volume":"14","author":"Luke","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Czarnecka, A.M., Bartnik, E., Fiedorowicz, M., and Rutkowski, P. (2020). Targeted Therapy in Melanoma and Mechanisms of Resistance. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21134576"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41568-019-0154-4","article-title":"Phenotype plasticity as enabler of melanoma progression and therapy resistance","volume":"19","author":"Arozarena","year":"2019","journal-title":"Nat. Rev. Cancer"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/PPO.0000000000000303","article-title":"Mechanisms of Resistance to PD-1 and PD-L1 Blockade","volume":"24","author":"Nowicki","year":"2018","journal-title":"Cancer J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cell.2017.01.017","article-title":"Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy","volume":"168","author":"Sharma","year":"2017","journal-title":"Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.bbcan.2019.02.002","article-title":"Many ways to resistance: How melanoma cells evade targeted therapies","volume":"1871","author":"Kozar","year":"2019","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ccr.2012.02.014","article-title":"Metabolic reprogramming: A cancer hallmark even warburg did not anticipate","volume":"21","author":"Ward","year":"2012","journal-title":"Cancer Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"eaaw5473","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e920957","DOI":"10.12659\/MSM.920957","article-title":"A Review of the Molecular Pathways Involved in Resistance to BRAF Inhibitors in Patients with Advanced-Stage Melanoma","volume":"26","author":"Tian","year":"2020","journal-title":"Med. Sci. Monit."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"937831","DOI":"10.3389\/fonc.2022.937831","article-title":"Changes in the Transcriptome and Chromatin Landscape in BRAFi-Resistant Melanoma Cells","volume":"12","author":"Reddi","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"102995","DOI":"10.1016\/j.critrevonc.2020.102995","article-title":"Metabolic rewiring in melanoma drug-resistant cells","volume":"153","author":"Bristot","year":"2020","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/pcmr.12661","article-title":"Metabolic strategies of melanoma cells: Mechanisms, interactions with the tumor microenvironment, and therapeutic implications","volume":"31","author":"Fischer","year":"2018","journal-title":"Pigment Cell Melanoma Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"722","DOI":"10.3389\/fonc.2020.00722","article-title":"Metabolic Plasticity of Melanoma Cells and Their Crosstalk with Tumor Microenvironment","volume":"10","author":"Avagliano","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.molmed.2014.12.007","article-title":"Molecular drivers of cellular metabolic reprogramming in melanoma","volume":"21","author":"Abildgaard","year":"2015","journal-title":"Trends Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"39473","DOI":"10.18632\/oncotarget.7790","article-title":"Mitochondrial oxidative phosphorylation controls cancer cell\u2019s life and death decisions upon exposure to MAPK inhibitors","volume":"7","author":"Guerreschi","year":"2016","journal-title":"Oncotarget"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.ccr.2012.11.020","article-title":"PGC1alpha expression defines a subset of human melanoma tumors with increased mitochondrial capacity and resistance to oxidative stress","volume":"23","author":"Vazquez","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41416-020-01159-y","article-title":"Mitochondrial oxidative phosphorylation in cutaneous melanoma","volume":"124","author":"Kumar","year":"2021","journal-title":"Br. J. Cancer"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.semcancer.2019.07.016","article-title":"Metabolic flexibility in melanoma: A potential therapeutic target","volume":"59","author":"Ruocco","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.semcdb.2019.05.001","article-title":"Targeting metabolic reprogramming in metastatic melanoma: The key role of nicotinamide phosphoribosyltransferase (NAMPT)","volume":"98","author":"Audrito","year":"2019","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Indini, A., Grossi, F., Mandala, M., Taverna, D., and Audrito, V. (2021). Metabolic Interplay between the Immune System and Melanoma Cells: Therapeutic Implications. Biomedicines, 9.","DOI":"10.3390\/biomedicines9060607"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1101\/gad.189365.112","article-title":"Links between metabolism and cancer","volume":"26","author":"Dang","year":"2012","journal-title":"Genes Dev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The Emerging Hallmarks of Cancer Metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.1200\/JCO.2009.23.4799","article-title":"Final version of 2009 AJCC melanoma staging and classification","volume":"27","author":"Balch","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2147\/ITT.S134842","article-title":"Melanoma treatment in review","volume":"7","author":"Domingues","year":"2018","journal-title":"Immunotargets Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"711","DOI":"10.1056\/NEJMoa1003466","article-title":"Improved survival with ipilimumab in patients with metastatic melanoma","volume":"363","author":"Hodi","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/S1470-2045(15)00083-2","article-title":"Pembrolizumab versus investigator-choice chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002): A randomised, controlled, phase 2 trial","volume":"16","author":"Ribas","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/S1470-2045(15)70076-8","article-title":"Nivolumab versus chemotherapy in patients with advanced melanoma who progressed after anti-CTLA-4 treatment (CheckMate 037): A randomised, controlled, open-label, phase 3 trial","volume":"16","author":"Weber","year":"2015","journal-title":"Lancet Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/S1470-2045(14)70012-9","article-title":"Safety and efficacy of vemurafenib in BRAF(V600E) and BRAF(V600K) mutation-positive melanoma (BRIM-3): Extended follow-up of a phase 3, randomised, open-label study","volume":"15","author":"McArthur","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/S0140-6736(15)60898-4","article-title":"Dabrafenib and trametinib versus dabrafenib and placebo for Val600 BRAF-mutant melanoma: A multicentre, double-blind, phase 3 randomised controlled trial","volume":"386","author":"Long","year":"2015","journal-title":"Lancet"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1158\/1078-0432.CCR-13-3122","article-title":"BRAF inhibitor resistance mechanisms in metastatic melanoma: Spectrum and clinical impact","volume":"20","author":"Rizos","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nrc.2016.2","article-title":"Acquired resistance to immunotherapy and future challenges","volume":"16","author":"Restifo","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1158\/1078-0432.CCR-17-2267","article-title":"Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Metastatic Melanoma","volume":"24","author":"Gide","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1056\/NEJMoa1200690","article-title":"Safety, activity, and immune correlates of anti-PD-1 antibody in cancer","volume":"366","author":"Topalian","year":"2012","journal-title":"N. Engl. J. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1126\/science.aaa4971","article-title":"Neoantigens in cancer immunotherapy","volume":"348","author":"Schumacher","year":"2015","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"LB-339","DOI":"10.1158\/1538-7445.AM2018-LB-339","article-title":"Abstract LB-339: Biomarkers predictive of response to pembrolizumab in head and neck cancer (HNSCC)","volume":"78","author":"Seiwert","year":"2018","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/annonc\/mdy507","article-title":"Immune biomarkers of response to immune-checkpoint inhibitors in head and neck squamous cell carcinoma","volume":"30","author":"Oliva","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1093\/jnci\/88.2.100","article-title":"Loss of functional beta 2-microglobulin in metastatic melanomas from five patients receiving immunotherapy","volume":"88","author":"Restifo","year":"1996","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1007\/s00262-018-2131-2","article-title":"Defective HLA class I antigen processing machinery in cancer","volume":"67","author":"Cai","year":"2018","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.molimm.2017.12.005","article-title":"The regulatory network behind MHC class I expression","volume":"113","author":"Jongsma","year":"2019","journal-title":"Mol. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"9864","DOI":"10.1073\/pnas.142298299","article-title":"Characterization of the expression of MHC proteins in human embryonic stem cells","volume":"99","author":"Drukker","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1007\/s00262-007-0402-4","article-title":"Histone deacetylase inhibitors induce TAP, LMP, Tapasin genes and MHC class I antigen presentation by melanoma cells","volume":"57","author":"Khan","year":"2008","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1158\/2159-8290.CD-15-1545","article-title":"Analysis of Immune Signatures in Longitudinal Tumor Samples Yields Insight into Biomarkers of Response and Mechanisms of Resistance to Immune Checkpoint Blockade","volume":"6","author":"Chen","year":"2016","journal-title":"Cancer Discov."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.cell.2017.09.050","article-title":"MHC-I Genotype Restricts the Oncogenic Mutational Landscape","volume":"171","author":"Marty","year":"2017","journal-title":"Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1158\/1541-7786.MCR-14-0450","article-title":"Interferon receptor signaling in malignancy: A network of cellular pathways defining biological outcomes","volume":"12","author":"Fish","year":"2014","journal-title":"Mol. Cancer Res."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2016.08.069","article-title":"Loss of IFN-gamma Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy","volume":"167","author":"Gao","year":"2016","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1056\/NEJMoa1604958","article-title":"Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma","volume":"375","author":"Zaretsky","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1158\/2326-6066.CIR-15-0097","article-title":"Progression of Lung Cancer Is Associated with Increased Dysfunction of T Cells Defined by Coexpression of Multiple Inhibitory Receptors","volume":"3","author":"Thommen","year":"2015","journal-title":"Cancer Immunol. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1126\/science.aae0491","article-title":"The epigenetic landscape of T cell exhaustion","volume":"354","author":"Sen","year":"2016","journal-title":"Science"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/j.immuni.2017.04.016","article-title":"Metabolic and Epigenetic Coordination of T Cell and Macrophage Immunity","volume":"46","author":"Phan","year":"2017","journal-title":"Immunity"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nature22367","article-title":"Chromatin states define tumour-specific T cell dysfunction and reprogramming","volume":"545","author":"Philip","year":"2017","journal-title":"Nature"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"E2480","DOI":"10.1073\/pnas.1305394110","article-title":"Strength of PD-1 signaling differentially affects T-cell effector functions","volume":"110","author":"Wei","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nri3862","article-title":"Molecular and cellular insights into T cell exhaustion","volume":"15","author":"Wherry","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1158\/2326-6066.CIR-15-0210","article-title":"PD-1 Blockade Expands Intratumoral Memory T Cells","volume":"4","author":"Ribas","year":"2016","journal-title":"Cancer Immunol. Res."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Indini, A., Massi, D., Pirro, M., Roila, F., Grossi, F., Sahebkar, A., Glodde, N., Bald, T., and Mandala, M. (2022). Targeting inflamed and non-inflamed melanomas: Biological background and clinical challenges. Semin. Cancer Biol.","DOI":"10.1016\/j.semcancer.2022.06.005"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.1172\/JCI91190","article-title":"IFN-gamma-related mRNA profile predicts clinical response to PD-1 blockade","volume":"127","author":"Ayers","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.coi.2016.05.006","article-title":"Monitoring immune responses in the tumor microenvironment","volume":"41","author":"Wargo","year":"2016","journal-title":"Curr. Opin. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.cell.2014.12.033","article-title":"Molecular and genetic properties of tumors associated with local immune cytolytic activity","volume":"160","author":"Rooney","year":"2015","journal-title":"Cell"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1016\/j.it.2016.09.006","article-title":"Dendritic Cells and Cancer Immunity","volume":"37","author":"Gardner","year":"2016","journal-title":"Trends Immunol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1016\/j.immuni.2018.09.024","article-title":"Successful Anti-PD-1 Cancer Immunotherapy Requires T Cell-Dendritic Cell Crosstalk Involving the Cytokines IFN-gamma and IL-12","volume":"49","author":"Garris","year":"2018","journal-title":"Immunity"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/s00262-011-1161-9","article-title":"Phenotype, function and clinical implications of myeloid-derived suppressor cells in cancer patients","volume":"61","author":"Filipazzi","year":"2012","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.cell.2006.01.007","article-title":"Macrophages: Obligate partners for tumor cell migration, invasion, and metastasis","volume":"124","author":"Condeelis","year":"2006","journal-title":"Cell"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.3390\/cancers6031670","article-title":"Tumor-associated macrophages as major players in the tumor microenvironment","volume":"6","author":"Chanmee","year":"2014","journal-title":"Cancers"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1126\/science.aaa6204","article-title":"T cell exclusion, immune privilege, and the tumor microenvironment","volume":"348","author":"Joyce","year":"2015","journal-title":"Science"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"984","DOI":"10.1016\/j.cell.2018.09.006","article-title":"A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade","volume":"175","author":"Shah","year":"2018","journal-title":"Cell"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1084\/jem.20140559","article-title":"VEGF-A modulates expression of inhibitory checkpoints on CD8+ T cells in tumors","volume":"212","author":"Voron","year":"2015","journal-title":"J. Exp. Med."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1038\/nm.3541","article-title":"Tumor endothelium FasL establishes a selective immune barrier promoting tolerance in tumors","volume":"20","author":"Motz","year":"2014","journal-title":"Nat. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/nature25501","article-title":"TGFbeta attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells","volume":"554","author":"Mariathasan","year":"2018","journal-title":"Nature"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7983","DOI":"10.1002\/jcp.27553","article-title":"Contribution of regulatory T cells to cancer: A review","volume":"234","author":"Najafi","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/nature14404","article-title":"Melanoma-intrinsic beta-catenin signalling prevents anti-tumour immunity","volume":"523","author":"Spranger","year":"2015","journal-title":"Nature"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5064","DOI":"10.1158\/1078-0432.CCR-13-3271","article-title":"Association of PD-1, PD-1 ligands, and other features of the tumor immune microenvironment with response to anti-PD-1 therapy","volume":"20","author":"Taube","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1016\/j.cmet.2016.08.011","article-title":"LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells","volume":"24","author":"Brand","year":"2016","journal-title":"Cell Metab."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1158\/0008-5472.CAN-16-2938","article-title":"Deletion of Lactate Dehydrogenase-A in Myeloid Cells Triggers Antitumor Immunity","volume":"77","author":"Seth","year":"2017","journal-title":"Cancer Res."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Daneshmandi, S., Wegiel, B., and Seth, P. (2019). Blockade of Lactate Dehydrogenase-A (LDH-A) Improves Efficacy of Anti-Programmed Cell Death-1 (PD-1) Therapy in Melanoma. Cancers, 11.","DOI":"10.3390\/cancers11040450"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Patel, H., Yacoub, N., Mishra, R., White, A., Long, Y., Alanazi, S., and Garrett, J.T. (2020). Current Advances in the Treatment of BRAF-Mutant Melanoma. Cancers, 12.","DOI":"10.3390\/cancers12020482"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.3892\/ijo.2016.3594","article-title":"Targeting the PI3K\/AKT\/mTOR pathway overcomes the stimulating effect of dabrafenib on the invasive behavior of melanoma cells with acquired resistance to the BRAF inhibitor","volume":"49","author":"Caporali","year":"2016","journal-title":"Int. J. Oncol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1158\/2159-8290.CD-13-0642","article-title":"Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy","volume":"4","author":"Shi","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2792","DOI":"10.1016\/j.ejca.2015.08.022","article-title":"Acquired BRAF inhibitor resistance: A multicenter meta-analysis of the spectrum and frequencies, clinical behaviour, and phenotypic associations of resistance mechanisms","volume":"51","author":"Johnson","year":"2015","journal-title":"Eur. J. Cancer"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"ra84","DOI":"10.1126\/scisignal.2001148","article-title":"BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation","volume":"3","author":"Corcoran","year":"2010","journal-title":"Sci. Signal."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1111\/cas.13156","article-title":"Hepatocyte growth factor\/MET in cancer progression and biomarker discovery","volume":"108","author":"Matsumoto","year":"2017","journal-title":"Cancer Sci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nature11183","article-title":"Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion","volume":"487","author":"Straussman","year":"2012","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"2876","DOI":"10.1158\/1535-7163.MCT-08-0431","article-title":"Increased cyclin D1 expression can mediate BRAF inhibitor resistance in BRAF V600E-mutated melanomas","volume":"7","author":"Smalley","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"10905","DOI":"10.18632\/oncotarget.23649","article-title":"Targeting the cyclin dependent kinase and retinoblastoma axis overcomes standard of care resistance in BRAF (V600E) -mutant melanoma","volume":"9","author":"Harris","year":"2018","journal-title":"Oncotarget"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/pcmr.12643","article-title":"Rare, yet relevant tumor cells-A new twist to melanoma cell plasticity","volume":"31","author":"Zingg","year":"2018","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Khaliq, M., and Fallahi-Sichani, M. (2019). Epigenetic Mechanisms of Escape from BRAF Oncogene Dependency. Cancers, 11.","DOI":"10.3390\/cancers11101480"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/nature22794","article-title":"Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance","volume":"546","author":"Shaffer","year":"2017","journal-title":"Nature"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1038\/jid.2014.418","article-title":"Epigenetic changes of EGFR have an important role in BRAF inhibitor-resistant cutaneous melanomas","volume":"135","author":"Wang","year":"2015","journal-title":"J. Investig. Dermatol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"13679","DOI":"10.1073\/pnas.1712064115","article-title":"Single-cell analysis resolves the cell state transition and signaling dynamics associated with melanoma drug-induced resistance","volume":"114","author":"Su","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"5712","DOI":"10.1038\/ncomms6712","article-title":"Low MITF\/AXL ratio predicts early resistance to multiple targeted drugs in melanoma","volume":"5","author":"Muller","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nm.4472","article-title":"Cooperative targeting of melanoma heterogeneity with an AXL antibody-drug conjugate and BRAF\/MEK inhibitors","volume":"24","author":"Boshuizen","year":"2018","journal-title":"Nat. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1158\/2159-8290.CD-12-0345","article-title":"Cancer cell metabolism: One hallmark, many faces","volume":"2","author":"Cantor","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1016\/j.cell.2015.08.016","article-title":"Metabolic Competition in the Tumor Microenvironment Is a Driver of Cancer Progression","volume":"162","author":"Chang","year":"2015","journal-title":"Cell"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"e1600200","DOI":"10.1126\/sciadv.1600200","article-title":"Fundamentals of cancer metabolism","volume":"2","author":"DeBerardinis","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1111\/imm.12777","article-title":"Metabolic reprogramming in the tumour microenvironment: A hallmark shared by cancer cells and T lymphocytes","volume":"152","author":"Allison","year":"2017","journal-title":"Immunology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1038\/ncb3124","article-title":"Metabolic pathways promoting cancer cell survival and growth","volume":"17","author":"Boroughs","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1085\/jgp.8.6.519","article-title":"The Metabolism of Tumors in the Body","volume":"8","author":"Warburg","year":"1927","journal-title":"J. Gen. Physiol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.3892\/ol.2012.928","article-title":"Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review)","volume":"4","author":"Zheng","year":"2012","journal-title":"Oncol. Lett."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.tibs.2015.12.001","article-title":"The Warburg Effect: How Does it Benefit Cancer Cells?","volume":"41","author":"Liberti","year":"2016","journal-title":"Trends Biochem. Sci."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"747001","DOI":"10.3389\/fphar.2021.747001","article-title":"Lactate Dehydrogenase A or B Knockdown Reduces Lactate Production and Inhibits Breast Cancer Cell Motility in vitro","volume":"12","author":"Khajah","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"6921","DOI":"10.1158\/0008-5472.CAN-11-1457","article-title":"Lactate: A metabolic key player in cancer","volume":"71","author":"Hirschhaeuser","year":"2011","journal-title":"Cancer Res."},{"key":"ref_112","first-page":"119","article-title":"Reexamining cancer metabolism: Lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect","volume":"38","author":"Brooks","year":"2017","journal-title":"Carcinogenesis"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1016\/j.bbabio.2010.10.012","article-title":"Choosing between glycolysis and oxidative phosphorylation: A tumor\u2019s dilemma?","volume":"1807","author":"Jose","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/cr.2017.155","article-title":"Mitochondrial metabolism and cancer","volume":"28","author":"Porporato","year":"2018","journal-title":"Cell Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1016\/j.cell.2016.07.002","article-title":"Mitochondria and Cancer","volume":"166","author":"Vyas","year":"2016","journal-title":"Cell"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nrc3803","article-title":"Mitochondrial ROS in cancer: Initiators, amplifiers or an Achilles\u2019 heel?","volume":"14","author":"Sabharwal","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1016\/j.molcel.2015.01.018","article-title":"Limited mitochondrial permeabilization causes DNA damage and genomic instability in the absence of cell death","volume":"57","author":"Ichim","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13578-020-00442-y","article-title":"Limited MOMP, ATM, and their roles in carcinogenesis and cancer treatment","volume":"10","author":"Bao","year":"2020","journal-title":"Cell Biosci."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"4617","DOI":"10.1038\/onc.2010.206","article-title":"Reversible acetylation of PGC-1: Connecting energy sensors and effectors to guarantee metabolic flexibility","volume":"29","author":"Jeninga","year":"2010","journal-title":"Oncogene"},{"key":"ref_120","first-page":"198","article-title":"The metabolic modulator PGC-1alpha in cancer","volume":"9","author":"Bost","year":"2019","journal-title":"Am. J. Cancer Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.canlet.2015.10.027","article-title":"Metabolic exchanges within tumor microenvironment","volume":"380","author":"Chiarugi","year":"2016","journal-title":"Cancer Lett."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3678","DOI":"10.1172\/JCI69600","article-title":"Glutamine and cancer: Cell biology, physiology, and clinical opportunities","volume":"123","author":"Hensley","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/j.trecan.2017.01.005","article-title":"Glutamine Metabolism in Cancer: Understanding the Heterogeneity","volume":"3","author":"Cluntun","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s00018-015-2070-4","article-title":"Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression","volume":"73","author":"Li","year":"2016","journal-title":"Cell Mol. Life Sci."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41416-019-0650-z","article-title":"Reprogramming of fatty acid metabolism in cancer","volume":"122","author":"Koundouros","year":"2020","journal-title":"Br. J. Cancer"},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1038\/nrc.2016.89","article-title":"The multifaceted roles of fatty acid synthesis in cancer","volume":"16","author":"Rohrig","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1038\/nrc.2016.87","article-title":"The metabolic fate of acetate in cancer","volume":"16","author":"Schug","year":"2016","journal-title":"Nat. Rev. Cancer"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40170-014-0027-y","article-title":"Acetate metabolism in cancer cells","volume":"2","author":"Hosios","year":"2014","journal-title":"Cancer Metab."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.tcb.2019.05.005","article-title":"Acetate Metabolism in Physiology, Cancer, and Beyond","volume":"29","author":"Bose","year":"2019","journal-title":"Trends Cell Biol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrclinonc.2016.60","article-title":"Cancer metabolism: A therapeutic perspective","volume":"14","author":"Pestell","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1038\/nrc2468","article-title":"Hypoxia, HIF1 and glucose metabolism in the solid tumour","volume":"8","author":"Denko","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1158\/2159-8290.CD-13-0440","article-title":"Response of BRAF-mutant melanoma to BRAF inhibition is mediated by a network of transcriptional regulators of glycolysis","volume":"4","author":"Parmenter","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"584","DOI":"10.18632\/oncotarget.965","article-title":"Dysfunctional oxidative phosphorylation makes malignant melanoma cells addicted to glycolysis driven by the (V600E)BRAF oncogene","volume":"4","author":"Hall","year":"2013","journal-title":"Oncotarget"},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"42626","DOI":"10.1074\/jbc.M111.282046","article-title":"Comparative metabolic flux profiling of melanoma cell lines: Beyond the Warburg effect","volume":"286","author":"Scott","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/onc.2016.198","article-title":"Metabolic rewiring in melanoma","volume":"36","author":"Ratnikov","year":"2017","journal-title":"Oncogene"},{"key":"ref_136","first-page":"52","article-title":"Lactate Contribution to the Tumor Microenvironment: Mechanisms, Effects on Immune Cells and Therapeutic Relevance","volume":"7","year":"2016","journal-title":"Front. Immunol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s10863-012-9428-1","article-title":"Role of monocarboxylate transporters in human cancers: State of the art","volume":"44","author":"Pinheiro","year":"2012","journal-title":"J. Bioenerg. Biomembr."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"62726","DOI":"10.18632\/oncotarget.10911","article-title":"Oncogenic regulation of tumor metabolic reprogramming","volume":"7","author":"Cascante","year":"2016","journal-title":"Oncotarget"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2257","DOI":"10.1158\/1078-0432.CCR-13-0898","article-title":"Molecular pathways: BRAF induces bioenergetic adaptation by attenuating oxidative phosphorylation","volume":"20","author":"Haq","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1016\/j.ccr.2013.02.003","article-title":"Oncogenic BRAF regulates oxidative metabolism via PGC1alpha and MITF","volume":"23","author":"Haq","year":"2013","journal-title":"Cancer Cell"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1038\/nature12154","article-title":"A key role for mitochondrial gatekeeper pyruvate dehydrogenase in oncogene-induced senescence","volume":"498","author":"Kaplon","year":"2013","journal-title":"Nature"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1158\/0008-5472.CAN-06-3312","article-title":"Mutant V600E BRAF increases hypoxia inducible factor-1alpha expression in melanoma","volume":"67","author":"Kumar","year":"2007","journal-title":"Cancer Res."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1016\/j.bbagen.2018.01.018","article-title":"Melanoma metabolism contributes to the cellular responses to MAPK\/ERK pathway inhibitors","volume":"1862","author":"Marchetti","year":"2018","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_144","doi-asserted-by":"crossref","unstructured":"Barbi de Moura, M., Vincent, G., Fayewicz, S.L., Bateman, N.W., Hood, B.L., Sun, M., Suhan, J., Duensing, S., Yin, Y., and Sander, C. (2012). Mitochondrial respiration--an important therapeutic target in melanoma. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040690"},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Jia, D., Park, J.H., Jung, K.H., Levine, H., and Kaipparettu, B.A. (2018). Elucidating the Metabolic Plasticity of Cancer: Mitochondrial Reprogramming and Hybrid Metabolic States. Cells, 7.","DOI":"10.3390\/cells7030021"},{"key":"ref_146","doi-asserted-by":"crossref","unstructured":"Soumoy, L., Schepkens, C., Krayem, M., Najem, A., Tagliatti, V., Ghanem, G.E., Saussez, S., Colet, J.M., and Journe, F. (2020). Metabolic Reprogramming in Metastatic Melanoma with Acquired Resistance to Targeted Therapies: Integrative Metabolomic and Proteomic Analysis. Cancers, 12.","DOI":"10.3390\/cancers12051323"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/s12943-017-0667-y","article-title":"ROS production induced by BRAF inhibitor treatment rewires metabolic processes affecting cell growth of melanoma cells","volume":"16","author":"Cesi","year":"2017","journal-title":"Mol. Cancer"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1208690","DOI":"10.1155\/2021\/1208690","article-title":"ROS as Regulators of Cellular Processes in Melanoma","volume":"2021","author":"Venza","year":"2021","journal-title":"Oxid Med. Cell Longev."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1186\/s12967-015-0581-2","article-title":"Vemurafenib resistance reprograms melanoma cells towards glutamine dependence","volume":"13","author":"Tran","year":"2015","journal-title":"J. Transl. Med."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nrc3340","article-title":"The NAD metabolome--a key determinant of cancer cell biology","volume":"12","author":"Chiarugi","year":"2012","journal-title":"Nat. Rev. Cancer"},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1038\/s41392-020-00311-7","article-title":"NAD(+) metabolism: Pathophysiologic mechanisms and therapeutic potential","volume":"5","author":"Xie","year":"2020","journal-title":"Signal. Transduct Target. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"704779","DOI":"10.3389\/fimmu.2021.704779","article-title":"The Extracellular NADome Modulates Immune Responses","volume":"12","author":"Audrito","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.3389\/fimmu.2019.01720","article-title":"NAD-Biosynthetic and Consuming Enzymes as Central Players of Metabolic Regulation of Innate and Adaptive Immune Responses in Cancer","volume":"10","author":"Audrito","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1038\/s41392-020-00354-w","article-title":"NAD(+) metabolism, stemness, the immune response, and cancer","volume":"6","author":"Navas","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"106189","DOI":"10.1016\/j.biocel.2022.106189","article-title":"NAMPT: A critical driver and therapeutic target for cancer","volume":"145","author":"Gasparrini","year":"2022","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Lin, T.C. (2022). Updated Functional Roles of NAMPT in Carcinogenesis and Therapeutic Niches. Cancers, 14.","DOI":"10.3390\/cancers14092059"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.cmet.2015.05.023","article-title":"NAD(+) Metabolism and the Control of Energy Homeostasis: A Balancing Act between Mitochondria and the Nucleus","volume":"22","author":"Canto","year":"2015","journal-title":"Cell Metab."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"3317","DOI":"10.1007\/s00018-020-03742-1","article-title":"Enzymology of extracellular NAD metabolism","volume":"78","author":"Gasparrini","year":"2021","journal-title":"Cell Mol. Life Sci."},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/nrendo.2015.117","article-title":"Physiological and pathophysiological roles of NAMPT and NAD metabolism","volume":"11","author":"Garten","year":"2015","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"358","DOI":"10.3389\/fonc.2020.00358","article-title":"NAMPT and NAPRT: Two Metabolic Enzymes with Key Roles in Inflammation","volume":"10","author":"Audrito","year":"2020","journal-title":"Front. Oncol."},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1514","DOI":"10.3389\/fonc.2019.01514","article-title":"Beyond Energy Metabolism: Exploiting the Additional Roles of NAMPT for Cancer Therapy","volume":"9","author":"Heske","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Van den Bergh, R., Morin, S., Sass, H.J., Grzesiek, S., Vekemans, M., Florence, E., Tran, H.T., Imiru, R.G., Heyndrickx, L., and Vanham, G. (2012). Monocytes contribute to differential immune pressure on R5 versus X4 HIV through the adipocytokine visfatin\/NAMPT. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035074"},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Torretta, S., Colombo, G., Travelli, C., Boumya, S., Lim, D., Genazzani, A.A., and Grolla, A.A. (2020). The Cytokine Nicotinamide Phosphoribosyltransferase (eNAMPT; PBEF; Visfatin) Acts as a Natural Antagonist of C-C Chemokine Receptor Type 5 (CCR5). Cells, 9.","DOI":"10.3390\/cells9020496"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1038\/s41586-021-03199-7","article-title":"Macrophages provide a transient muscle stem cell niche via NAMPT secretion","volume":"591","author":"Ratnayake","year":"2021","journal-title":"Nature"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"13135","DOI":"10.1038\/srep13135","article-title":"Unique Toll-Like Receptor 4 Activation by NAMPT\/PBEF Induces NFkappaB Signaling and Inflammatory Lung Injury","volume":"5","author":"Camp","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/cphy.c160029","article-title":"Regulation and Function of Extracellular Nicotinamide Phosphoribosyltransferase\/Visfatin","volume":"7","author":"Carbone","year":"2017","journal-title":"Compr. Physiol."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"4116","DOI":"10.1038\/s41467-019-12055-2","article-title":"Extracellular nicotinate phosphoribosyltransferase binds Toll like receptor 4 and mediates inflammation","volume":"10","author":"Manago","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"5386","DOI":"10.1038\/s41598-020-62190-w","article-title":"Visfatin\/eNampt induces endothelial dysfunction in vivo: A role for Toll-Like Receptor 4 and NLRP3 inflammasome","volume":"10","author":"Romacho","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1038\/s41586-019-1150-2","article-title":"NAD metabolic dependency in cancer is shaped by gene amplification and enhancer remodelling","volume":"569","author":"Chowdhry","year":"2019","journal-title":"Nature"},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.metabol.2018.01.001","article-title":"The role of extracellular and intracellular Nicotinamide phosphoribosyl-transferase in cancer: Diagnostic and therapeutic perspectives and challenges","volume":"82","author":"Dalamaga","year":"2018","journal-title":"Metabolism"},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1186\/s12967-022-03315-9","article-title":"Tumors carrying BRAF-mutations over-express NAMPT that is genetically amplified and possesses oncogenic properties","volume":"20","author":"Audrito","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"6123","DOI":"10.2174\/138161212803582531","article-title":"Nampt\/Visfatin\/PBEF: A functionally multi-faceted protein with a pivotal role in malignant tumors","volume":"18","author":"Jieyu","year":"2012","journal-title":"Curr. Pharm. Des."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.pharmthera.2015.02.004","article-title":"Inhibition of nicotinamide phosphoribosyltransferase (NAMPT) as a therapeutic strategy in cancer","volume":"151","author":"Sampath","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"99514","DOI":"10.18632\/oncotarget.20577","article-title":"NAMPT overexpression induces cancer stemness and defines a novel tumor signature for glioma prognosis","volume":"8","author":"Carnero","year":"2017","journal-title":"Oncotarget"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1158\/1078-0432.CCR-17-2575","article-title":"NAMPT Is a Potent Oncogene in Colon Cancer Progression that Modulates Cancer Stem Cell Properties and Resistance to Therapy through Sirt1 and PARP","volume":"24","author":"Carnero","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_176","first-page":"503","article-title":"Increased Nicotinamide Phosphoribosyltransferase in Rhabdomyosarcomas and Leiomyosarcomas Compared to Skeletal and Smooth Muscle Tissue","volume":"36","author":"Vora","year":"2016","journal-title":"Anticancer. Res."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"7434","DOI":"10.1158\/1078-0432.CCR-04-0548","article-title":"Gene expression profile associated with response to doxorubicin-based therapy in breast cancer","volume":"11","author":"Folgueira","year":"2005","journal-title":"Clin. Cancer Res."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"23409","DOI":"10.1002\/jcp.28910","article-title":"NAMPT regulates PKM2 nuclear location through 14-3-3zeta: Conferring resistance to tamoxifen in breast cancer","volume":"234","author":"Ge","year":"2019","journal-title":"J. Cell Physiol."},{"key":"ref_179","doi-asserted-by":"crossref","unstructured":"Audrito, V., Manago, A., La Vecchia, S., Zamporlini, F., Vitale, N., Baroni, G., Cignetto, S., Serra, S., Bologna, C., and Stingi, A. (2018). Nicotinamide Phosphoribosyltransferase (NAMPT) as a Therapeutic Target in BRAF-Mutated Metastatic Melanoma. J. Natl. Cancer Inst., 110.","DOI":"10.1093\/jnci\/djx198"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/onc.2010.468","article-title":"NAMPT overexpression in prostate cancer and its contribution to tumor cell survival and stress response","volume":"30","author":"Wang","year":"2011","journal-title":"Oncogene"},{"key":"ref_181","doi-asserted-by":"crossref","unstructured":"Bolandghamat Pour, Z., Nourbakhsh, M., Mousavizadeh, K., Madjd, Z., Ghorbanhosseini, S.S., Abdolvahabi, Z., Hesari, Z., and Ezzati Mobasser, S. (2019). Suppression of nicotinamide phosphoribosyltransferase expression by miR-154 reduces the viability of breast cancer cells and increases their susceptibility to doxorubicin. BMC Cancer, 19.","DOI":"10.1186\/s12885-019-6221-0"},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"4102","DOI":"10.1158\/0008-5472.CAN-16-2263","article-title":"The Alkylating Chemotherapeutic Temozolomide Induces Metabolic Stress in IDH1-Mutant Cancers and Potentiates NAD(+) Depletion-Mediated Cytotoxicity","volume":"77","author":"Tateishi","year":"2017","journal-title":"Cancer Res."},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.leukres.2018.04.004","article-title":"Inhibition of NAMPT sensitizes MOLT4 leukemia cells for etoposide treatment through the SIRT2-p53 pathway","volume":"69","author":"Grohmann","year":"2018","journal-title":"Leuk Res."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1182\/blood-2013-02-483511","article-title":"Intracellular NAD(+) depletion enhances bortezomib-induced anti-myeloma activity","volume":"122","author":"Cagnetta","year":"2013","journal-title":"Blood"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1182\/blood-2018-05-850826","article-title":"IDH2 inhibition enhances proteasome inhibitor responsiveness in hematological malignancies","volume":"133","author":"Bergaggio","year":"2018","journal-title":"Blood"},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/j.bbrc.2012.03.088","article-title":"Sirtuin inhibition attenuates the production of inflammatory cytokines in lipopolysaccharide-stimulated macrophages","volume":"420","author":"Fernandes","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"109516","DOI":"10.1016\/j.celrep.2021.109516","article-title":"NAD(+) supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells","volume":"36","author":"Wang","year":"2021","journal-title":"Cell Rep."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1038\/s41556-019-0287-4","article-title":"NAD(+) metabolism governs the proinflammatory senescence-associated secretome","volume":"21","author":"Nacarelli","year":"2019","journal-title":"Nat. Cell Biol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/j.cell.2020.02.035","article-title":"Propionic Acid Shapes the Multiple Sclerosis Disease Course by an Immunomodulatory Mechanism","volume":"180","author":"Duscha","year":"2020","journal-title":"Cell"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"656","DOI":"10.3389\/fphar.2020.00656","article-title":"Recent Advances in NAMPT Inhibitors: A Novel Immunotherapic Strategy","volume":"11","author":"Galli","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.jmb.2006.06.082","article-title":"Crystal structure of visfatin\/pre-B cell colony-enhancing factor 1\/nicotinamide phosphoribosyltransferase, free and in complex with the anti-cancer agent FK-866","volume":"362","author":"Kim","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1016\/j.phrs.2016.10.027","article-title":"NAD(+) salvage pathway in cancer metabolism and therapy","volume":"114","author":"Kennedy","year":"2016","journal-title":"Pharmacol. Res."},{"key":"ref_193","doi-asserted-by":"crossref","unstructured":"Ghanem, M.S., Monacelli, F., and Nencioni, A. (2021). Advances in NAD-Lowering Agents for Cancer Treatment. Nutrients, 13.","DOI":"10.3390\/nu13051665"},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"5872","DOI":"10.1128\/MCB.00112-09","article-title":"The small molecule GMX1778 is a potent inhibitor of NAD+ biosynthesis: Strategy for enhanced therapy in nicotinic acid phosphoribosyltransferase 1-deficient tumors","volume":"29","author":"Watson","year":"2009","journal-title":"Mol. Cell Biol."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1007\/s00280-009-1125-3","article-title":"Safety and efficacy of NAD depleting cancer drugs: Results of a phase I clinical trial of CHS 828 and overview of published data","volume":"65","author":"Berglund","year":"2010","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1593\/neo.131304","article-title":"Dependence of tumor cell lines and patient-derived tumors on the NAD salvage pathway renders them sensitive to NAMPT inhibition with GNE-618","volume":"15","author":"Xiao","year":"2013","journal-title":"Neoplasia"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"1352","DOI":"10.1016\/j.chembiol.2013.09.014","article-title":"Next-generation NAMPT inhibitors identified by sequential high-throughput phenotypic chemical and functional genomic screens","volume":"20","author":"Matheny","year":"2013","journal-title":"Chem. Biol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1093\/toxsci\/kfu268","article-title":"Retinal toxicity, in vivo and in vitro, associated with inhibition of nicotinamide phosphoribosyltransferase","volume":"144","author":"Zabka","year":"2015","journal-title":"Toxicol. Sci."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"111576","DOI":"10.1016\/j.ejmech.2019.111576","article-title":"Identification of potent triazolylpyridine nicotinamide phosphoribosyltransferase (NAMPT) inhibitors bearing a 1,2,3-triazole tail group","volume":"181","author":"Travelli","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"105034","DOI":"10.1016\/j.dib.2019.105034","article-title":"Data on metabolic stability, aqueous solubility and CYP inhibition of novel triazole-based nicotinamide phosphoribosyltransferase (NAMPT) inhibitors","volume":"28","author":"Aprile","year":"2020","journal-title":"Data Brief."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1038\/aps.2017.80","article-title":"Crystal structure-based comparison of two NAMPT inhibitors","volume":"39","author":"Zhang","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"10043","DOI":"10.1038\/srep10043","article-title":"Discovery and characterization of novel small-molecule inhibitors targeting nicotinamide phosphoribosyltransferase","volume":"5","author":"Xu","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1158\/1535-7163.MCT-16-0197","article-title":"Dual and Specific Inhibition of NAMPT and PAK4 By KPT-9274 Decreases Kidney Cancer Growth","volume":"15","author":"Chen","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"42555","DOI":"10.1038\/srep42555","article-title":"A novel orally bioavailable compound KPT-9274 inhibits PAK4, and blocks triple negative breast cancer tumor growth","volume":"7","author":"Rane","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"1828","DOI":"10.1038\/s41375-019-0692-5","article-title":"OT-82, a novel anticancer drug candidate that targets the strong dependence of hematological malignancies on NAD biosynthesis","volume":"34","author":"Korotchkina","year":"2020","journal-title":"Leukemia"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1158\/1538-7445.AM2018-5477","article-title":"Abstract 5477: Targeting nicotinamide phosphoribosyltransferase (NAMPT) with OT-82 in Ewing sarcoma","volume":"78","author":"Gibson","year":"2018","journal-title":"Cancer Res."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.1038\/s41375-019-0683-6","article-title":"Effective targeting of NAMPT in patient-derived xenograft models of high-risk pediatric acute lymphoblastic leukemia","volume":"34","author":"Somers","year":"2020","journal-title":"Leukemia"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"797","DOI":"10.1111\/j.1365-2133.2011.10239.x","article-title":"Noninvasive genomic detection of melanoma","volume":"164","author":"Wachsman","year":"2011","journal-title":"Br. J. Dermatol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/pcmr.12037","article-title":"Nicotinamide phosphoribosyltransferase (NAMPT) is over-expressed in melanoma lesions","volume":"26","author":"Maldi","year":"2013","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.bbrc.2017.09.071","article-title":"The NAMPT\/E2F2\/SIRT1 axis promotes proliferation and inhibits p53-dependent apoptosis in human melanoma cells","volume":"493","author":"Zhao","year":"2017","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1111\/pcmr.12420","article-title":"Nicotinamide phosphoribosyltransferase (NAMPT\/PBEF\/visfatin) is a tumoural cytokine released from melanoma","volume":"28","author":"Grolla","year":"2015","journal-title":"Pigment. Cell Melanoma Res."},{"key":"ref_212","doi-asserted-by":"crossref","unstructured":"Audrito, V., Messana, V.G., Moiso, E., Vitale, N., Arruga, F., Brandimarte, L., Gaudino, F., Pellegrino, E., Vaisitti, T., and Riganti, C. (2020). NAMPT Over-Expression Recapitulates the BRAF Inhibitor Resistant Phenotype Plasticity in Melanoma. Cancers, 12.","DOI":"10.3390\/cancers12123855"},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"3519","DOI":"10.1182\/blood-2012-03-416776","article-title":"Targeting NAD+ salvage pathway induces autophagy in multiple myeloma cells via mTORC1 and extracellular signal-regulated kinase (ERK1\/2) inhibition","volume":"120","author":"Cea","year":"2012","journal-title":"Blood"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1101\/gad.305854.117","article-title":"Pivotal role of NAMPT in the switch of melanoma cells toward an invasive and drug-resistant phenotype","volume":"32","author":"Ohanna","year":"2018","journal-title":"Genes Dev."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"18997","DOI":"10.18632\/oncotarget.24871","article-title":"Extracellular nicotinamide phosphoribosyltransferase (eNAMPT) is a novel marker for patients with BRAF-mutated metastatic melanoma","volume":"9","author":"Audrito","year":"2018","journal-title":"Oncotarget"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1182\/blood-2014-07-589069","article-title":"Extracellular nicotinamide phosphoribosyltransferase (NAMPT) promotes M2 macrophage polarization in chronic lymphocytic leukemia","volume":"125","author":"Audrito","year":"2015","journal-title":"Blood"},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.phrs.2018.06.022","article-title":"NAMPT: A pleiotropic modulator of monocytes and macrophages","volume":"135","author":"Travelli","year":"2018","journal-title":"Pharmacol. Res."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1938","DOI":"10.1158\/0008-5472.CAN-18-1544","article-title":"Nicotinamide Phosphoribosyltransferase (NAMPT) acts as a metabolic gate for mobilization of myeloid-derived suppressor cells","volume":"79","author":"Travelli","year":"2019","journal-title":"Cancer Res."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1002\/ijc.31808","article-title":"NAMPT signaling is critical for the proangiogenic activity of tumor-associated neutrophils","volume":"144","author":"Pylaeva","year":"2019","journal-title":"Int. J. Cancer"},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.cmet.2020.10.021","article-title":"NAD(+) Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion","volume":"33","author":"Lv","year":"2021","journal-title":"Cell Metab."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1038\/s41467-021-22923-5","article-title":"A Stat1 bound enhancer promotes Nampt expression and function within tumor associated macrophages","volume":"12","author":"Huffaker","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"104147","DOI":"10.1016\/j.isci.2022.104147","article-title":"Extracellular nicotinamide phosphoribosyltransferase boosts IFNgamma-induced macrophage polarization independently of TLR4","volume":"25","author":"Colombo","year":"2022","journal-title":"iScience"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1016\/j.cell.2015.07.061","article-title":"Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance","volume":"162","author":"Hugo","year":"2015","journal-title":"Cell"},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"832","DOI":"10.1158\/2159-8290.CD-16-0955","article-title":"Biomarker Accessible and Chemically Addressable Mechanistic Subtypes of BRAF Melanoma","volume":"7","author":"Eskiocak","year":"2017","journal-title":"Cancer Discov."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1165\/rcmb.2017-0155OC","article-title":"Novel Mechanism for Nicotinamide Phosphoribosyltransferase Inhibition of TNF-alpha-mediated Apoptosis in Human Lung Endothelial Cells","volume":"59","author":"Oita","year":"2018","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"103059","DOI":"10.1016\/j.ebiom.2020.103059","article-title":"Role of secreted extracellular nicotinamide phosphoribosyltransferase (eNAMPT) in prostate cancer progression: Novel biomarker and therapeutic target","volume":"61","author":"Sun","year":"2020","journal-title":"EBioMedicine"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1165\/rcmb.2021-0357OC","article-title":"eNAMPT is a Novel DAMP that Contributes to the Severity of Radiation-Induced Lung Fibrosis","volume":"66","author":"Garcia","year":"2022","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"2002536","DOI":"10.1183\/13993003.02536-2020","article-title":"Endothelial eNAMPT Amplifies Preclinical Acute Lung Injury: Efficacy of an eNAMPT-Neutralising mAb","volume":"57","author":"Quijada","year":"2020","journal-title":"Eur. Respir. J."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1007\/s00109-020-01892-0","article-title":"Neutralization of extracellular NAMPT (nicotinamide phosphoribosyltransferase) ameliorates experimental murine colitis","volume":"98","author":"Colombo","year":"2020","journal-title":"J. Mol. Med."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"101669","DOI":"10.1016\/j.jbc.2022.101669","article-title":"Molecular insights into the interaction between human nicotinamide phosphoribosyltransferase and Toll-like receptor 4","volume":"298","author":"Gasparrini","year":"2022","journal-title":"J. Biol. Chem."},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S1097-2765(03)00114-X","article-title":"GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR","volume":"11","author":"Kim","year":"2003","journal-title":"Mol. Cell"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1016\/j.cell.2009.03.046","article-title":"DEPTOR is an mTOR inhibitor frequently overexpressed in multiple myeloma cells and required for their survival","volume":"137","author":"Peterson","year":"2009","journal-title":"Cell"},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/S0092-8674(02)00808-5","article-title":"mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery","volume":"110","author":"Kim","year":"2002","journal-title":"Cell"},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"316","DOI":"10.1038\/ncb1547","article-title":"Insulin signalling to mTOR mediated by the Akt\/PKB substrate PRAS40","volume":"9","author":"Lee","year":"2007","journal-title":"Nat. Cell Biol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1126\/science.1157535","article-title":"The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1","volume":"320","author":"Sancak","year":"2008","journal-title":"Science"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"3242","DOI":"10.1038\/emboj.2011.257","article-title":"Regulation of TFEB and V-ATPases by mTORC1","volume":"30","author":"Schwartz","year":"2011","journal-title":"EMBO J."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.cell.2011.06.034","article-title":"mTOR complex 1 regulates lipin 1 localization to control the SREBP pathway","volume":"146","author":"Peterson","year":"2011","journal-title":"Cell"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition, growth, ageing and disease","volume":"21","author":"Liu","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1038\/nrm3025","article-title":"mTOR: From growth signal integration to cancer, diabetes and ageing","volume":"12","author":"Zoncu","year":"2011","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"1965","DOI":"10.1016\/j.bbamcr.2011.03.013","article-title":"Interplay between FOXO, TOR, and Akt","volume":"1813","author":"Hay","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1152\/physrev.00026.2020","article-title":"Regulation and metabolic functions of mTORC1 and mTORC2","volume":"101","author":"Szwed","year":"2021","journal-title":"Physiol. Rev."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"8204","DOI":"10.1073\/pnas.0502857102","article-title":"The coordinate regulation of the p53 and mTOR pathways in cells","volume":"102","author":"Feng","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.cell.2008.06.028","article-title":"p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling","volume":"134","author":"Budanov","year":"2008","journal-title":"Cell"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"29655","DOI":"10.1074\/jbc.M212770200","article-title":"A novel hypoxia-inducible factor-independent hypoxic response regulating mammalian target of rapamycin and its targets","volume":"278","author":"Arsham","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1101\/gad.1617608","article-title":"Hypoxia regulates TSC1\/2-mTOR signaling and tumor suppression through REDD1-mediated 14-3-3 shuttling","volume":"22","author":"DeYoung","year":"2008","journal-title":"Genes Dev."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1042\/BJ20081668","article-title":"mTOR complex 2 (mTORC2) controls hydrophobic motif phosphorylation and activation of serum- and glucocorticoid-induced protein kinase 1 (SGK1)","volume":"416","author":"Alessi","year":"2008","journal-title":"Biochem. J."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"1919","DOI":"10.1038\/emboj.2008.119","article-title":"Essential function of TORC2 in PKC and Akt turn motif phosphorylation, maturation and signalling","volume":"27","author":"Ikenoue","year":"2008","journal-title":"EMBO J."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1083\/jcb.201610060","article-title":"Localization of mTORC2 activity inside cells","volume":"216","author":"Ebner","year":"2017","journal-title":"J. Cell Biol."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.cmet.2013.04.010","article-title":"Dynamic adipocyte phosphoproteome reveals that Akt directly regulates mTORC2","volume":"17","author":"Humphrey","year":"2013","journal-title":"Cell Metab."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.tem.2019.09.005","article-title":"Growth Factor-Dependent and -Independent Activation of mTORC2","volume":"31","author":"Knudsen","year":"2020","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.semcancer.2019.07.003","article-title":"mTOR: Role in cancer, metastasis and drug resistance","volume":"59","author":"Murugan","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"17414","DOI":"10.1073\/pnas.0809136105","article-title":"Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation","volume":"105","author":"Choo","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_254","doi-asserted-by":"crossref","unstructured":"El Hage, A., and Dormond, O. (2021). Combining mTOR Inhibitors and T Cell-Based Immunotherapies in Cancer Treatment. Cancers, 13.","DOI":"10.3390\/cancers13061359"},{"key":"ref_255","doi-asserted-by":"crossref","unstructured":"Feldman, M.E., Apsel, B., Uotila, A., Loewith, R., Knight, Z.A., Ruggero, D., and Shokat, K.M. (2009). Active-site inhibitors of mTOR target rapamycin-resistant outputs of mTORC1 and mTORC2. PLoS Biol., 7.","DOI":"10.1371\/journal.pbio.1000038"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/978-1-61779-430-8_29","article-title":"Development of ATP-competitive mTOR inhibitors","volume":"821","author":"Liu","year":"2012","journal-title":"Methods Mol. Biol."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"283","DOI":"10.2174\/1574892811666160519113731","article-title":"Review of PI3K\/mTOR Inhibitors Entering Clinical Trials to Treat Triple Negative Breast Cancers","volume":"11","author":"Fouque","year":"2016","journal-title":"Recent Pat. Anticancer Drug Discov."},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/nature17963","article-title":"Overcoming mTOR resistance mutations with a new-generation mTOR inhibitor","volume":"534","author":"Okaniwa","year":"2016","journal-title":"Nature"},{"key":"ref_259","first-page":"1069","article-title":"Mechanistic target of rapamycin inhibitors: Successes and challenges as cancer therapeutics","volume":"2","author":"Bhaoighill","year":"2019","journal-title":"Cancer Drug Resist."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/cncr.21265","article-title":"CCI-779 in metastatic melanoma: A phase II trial of the California Cancer Consortium","volume":"104","author":"Margolin","year":"2005","journal-title":"Cancer"},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1172\/JCI44145","article-title":"Next-generation mTOR inhibitors in clinical oncology: How pathway complexity informs therapeutic strategy","volume":"121","author":"Wander","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1726078","DOI":"10.1155\/2017\/1726078","article-title":"Resistance to mTORC1 Inhibitors in Cancer Therapy: From Kinase Mutations to Intratumoral Heterogeneity of Kinase Activity","volume":"2017","author":"Faes","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1016\/j.molcel.2017.06.033","article-title":"Focal Adhesion- and IGF1R-Dependent Survival and Migratory Pathways Mediate Tumor Resistance to mTORC1\/2 Inhibition","volume":"67","author":"Yoon","year":"2017","journal-title":"Mol. Cell"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.molcel.2008.02.024","article-title":"PKBalpha\/Akt1 acts downstream of DNA-PK in the DNA double-strand break response and promotes survival","volume":"30","author":"Bozulic","year":"2008","journal-title":"Mol. Cell"},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.molcel.2011.01.019","article-title":"TBK1 directly engages Akt\/PKB survival signaling to support oncogenic transformation","volume":"41","author":"Ou","year":"2011","journal-title":"Mol. Cell"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"6474","DOI":"10.1073\/pnas.1016132108","article-title":"IkappaB kinase epsilon and TANK-binding kinase 1 activate AKT by direct phosphorylation","volume":"108","author":"Xie","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_267","first-page":"1506","article-title":"The Complex Role of Autophagy in Melanoma Evolution: New Perspectives from Mouse Models","volume":"9","author":"Bodemeyer","year":"2019","journal-title":"Front. Oncol."},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1158\/2159-8290.CD-14-1473","article-title":"Atg7 Overcomes Senescence and Promotes Growth of BrafV600E-Driven Melanoma","volume":"5","author":"Xie","year":"2015","journal-title":"Cancer Discov."},{"key":"ref_269","doi-asserted-by":"crossref","unstructured":"Centonze, G., Centonze, S., Ponzone, L., and Calautti, E. (2022). ROCK \u2018n TOR: An Outlook on Keratinocyte Stem Cell Expansion in Regenerative Medicine via Protein Kinase Inhibition. Cells, 11.","DOI":"10.3390\/cells11071130"},{"key":"ref_270","doi-asserted-by":"crossref","unstructured":"Janowska, A., Iannone, M., Fidanzi, C., Romanelli, M., Filippi, L., Del Re, M., Martins, M., and Dini, V. (2022). The Genetic Basis of Dormancy and Awakening in Cutaneous Metastatic Melanoma. Cancers, 14.","DOI":"10.3390\/cancers14092104"},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1158\/1078-0432.CCR-15-1110","article-title":"Analysis of mTOR Gene Aberrations in Melanoma Patients and Evaluation of Their Sensitivity to PI3K-AKT-mTOR Pathway Inhibitors","volume":"22","author":"Kong","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1056\/NEJMra033540","article-title":"Immunosuppressive drugs for kidney transplantation","volume":"351","author":"Halloran","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.it.2014.10.006","article-title":"Intersection of mTOR and STAT signaling in immunity","volume":"36","author":"Saleiro","year":"2015","journal-title":"Trends Immunol."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1074\/jbc.M607365200","article-title":"Regulatory effects of mammalian target of rapamycin-activated pathways in type I and II interferon signaling","volume":"282","author":"Kaur","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1146\/annurev-immunol-020711-075024","article-title":"Regulation of immune responses by mTOR","volume":"30","author":"Powell","year":"2012","journal-title":"Annu. Rev. Immunol."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"774103","DOI":"10.3389\/fimmu.2021.774103","article-title":"mTOR-Mediated Regulation of Immune Responses in Cancer and Tumor Microenvironment","volume":"12","author":"Mafi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ncb839","article-title":"TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling","volume":"4","author":"Inoki","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cell.2005.02.031","article-title":"Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis","volume":"121","author":"Ma","year":"2005","journal-title":"Cell"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S1097-2765(02)00568-3","article-title":"Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase\/akt pathway","volume":"10","author":"Manning","year":"2002","journal-title":"Mol. Cell"},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"5771","DOI":"10.1038\/onc.2017.189","article-title":"Melanocytic nevi and melanoma: Unraveling a complex relationship","volume":"36","author":"Damsky","year":"2017","journal-title":"Oncogene"},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/sj.jid.5701074","article-title":"mTOR is activated in the majority of malignant melanomas","volume":"128","author":"Karbowniczek","year":"2008","journal-title":"J. Investig. Dermatol."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1016\/j.ccr.2006.10.003","article-title":"A negative feedback signaling network underlies oncogene-induced senescence","volume":"10","author":"Reczek","year":"2006","journal-title":"Cancer Cell"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"E317","DOI":"10.1073\/pnas.1614684114","article-title":"Dual-specificity phosphatase 5 controls the localized inhibition, propagation, and transforming potential of ERK signaling","volume":"114","author":"Kidger","year":"2017","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1101\/gad.187252.112","article-title":"Abrogation of BRAFV600E-induced senescence by PI3K pathway activation contributes to melanomagenesis","volume":"26","author":"Vredeveld","year":"2012","journal-title":"Genes Dev."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1038\/ng.356","article-title":"Braf(V600E) cooperates with Pten loss to induce metastatic melanoma","volume":"41","author":"Dankort","year":"2009","journal-title":"Nat. Genet."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.ccr.2009.02.022","article-title":"Oncogenic Braf induces melanocyte senescence and melanoma in mice","volume":"15","author":"Dhomen","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1038\/onc.2009.95","article-title":"Melanocytic nevus-like hyperplasia and melanoma in transgenic BRAFV600E mice","volume":"28","author":"Goel","year":"2009","journal-title":"Oncogene"},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.ccell.2014.11.014","article-title":"mTORC1 activation blocks BrafV600E-induced growth arrest but is insufficient for melanoma formation","volume":"27","author":"Damsky","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.ccell.2014.12.005","article-title":"mTOR signaling in melanoma: Oncogene-induced pseudo-senescence?","volume":"27","author":"Souroullas","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1038\/ng.2359","article-title":"Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma","volume":"44","author":"Krauthammer","year":"2012","journal-title":"Nat. Genet."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1016\/j.celrep.2016.02.010","article-title":"DNMT3b Modulates Melanoma Growth by Controlling Levels of mTORC2 Component RICTOR","volume":"14","author":"Micevic","year":"2016","journal-title":"Cell Rep."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1016\/j.ccr.2010.11.023","article-title":"Acquired resistance to BRAF inhibitors mediated by a RAF kinase switch in melanoma can be overcome by cotargeting MEK and IGF-1R\/PI3K","volume":"18","author":"Villanueva","year":"2010","journal-title":"Cancer Cell"},{"key":"ref_293","doi-asserted-by":"crossref","unstructured":"Atefi, M., von Euw, E., Attar, N., Ng, C., Chu, C., Guo, D., Nazarian, R., Chmielowski, B., Glaspy, J.A., and Comin-Anduix, B. (2011). Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT\/mTOR pathway. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0028973"},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1158\/2159-8290.CD-13-0279","article-title":"A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition","volume":"4","author":"Shi","year":"2014","journal-title":"Cancer Discov."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1038\/nature09626","article-title":"Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation","volume":"468","author":"Nazarian","year":"2010","journal-title":"Nature"},{"key":"ref_296","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nature13121","article-title":"Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma","volume":"508","author":"Sun","year":"2014","journal-title":"Nature"},{"key":"ref_297","doi-asserted-by":"crossref","unstructured":"Chen, B., Tardell, C., Higgins, B., Packman, K., Boylan, J.F., and Niu, H. (2012). BRAFV600E negatively regulates the AKT pathway in melanoma cell lines. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042598"},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"196ra198","DOI":"10.1126\/scitranslmed.3005753","article-title":"TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF-mutant melanoma","volume":"5","author":"Corcoran","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"5067","DOI":"10.1158\/0008-5472.CAN-11-0140","article-title":"Combinatorial treatments that overcome PDGFRbeta-driven resistance of melanoma cells to V600EB-RAF inhibition","volume":"71","author":"Shi","year":"2011","journal-title":"Cancer Res."},{"key":"ref_300","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1158\/1535-7163.MCT-11-0989","article-title":"Combinations of BRAF, MEK, and PI3K\/mTOR inhibitors overcome acquired resistance to the BRAF inhibitor GSK2118436 dabrafenib, mediated by NRAS or MEK mutations","volume":"11","author":"Greger","year":"2012","journal-title":"Mol. Cancer Ther."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"7037","DOI":"10.1158\/0008-5472.CAN-14-1392","article-title":"Inhibition of mTORC1\/2 overcomes resistance to MAPK pathway inhibitors mediated by PGC1alpha and oxidative phosphorylation in melanoma","volume":"74","author":"Gopal","year":"2014","journal-title":"Cancer Res."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"1834","DOI":"10.1172\/JCI82661","article-title":"Targeting mitochondrial biogenesis to overcome drug resistance to MAPK inhibitors","volume":"126","author":"Zhang","year":"2016","journal-title":"J. Clin. Investig."},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1016\/j.cmet.2013.10.001","article-title":"mTORC1 controls mitochondrial activity and biogenesis through 4E-BP-dependent translational regulation","volume":"18","author":"Morita","year":"2013","journal-title":"Cell Metab."},{"key":"ref_304","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.molcel.2012.05.043","article-title":"Glutaminolysis activates Rag-mTORC1 signaling","volume":"47","author":"Duran","year":"2012","journal-title":"Mol. Cell"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1038\/onc.2010.539","article-title":"Genome-wide shRNA screen reveals increased mitochondrial dependence upon mTORC2 addiction","volume":"30","author":"Colombi","year":"2011","journal-title":"Oncogene"},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"744","DOI":"10.1038\/s41568-018-0074-8","article-title":"mTOR signalling and cellular metabolism are mutual determinants in cancer","volume":"18","author":"Mossmann","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1096\/fj.13-237743","article-title":"Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2)","volume":"28","author":"Lamming","year":"2014","journal-title":"FASEB J."},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.cmet.2020.08.011","article-title":"Glutamine Metabolism Controls Stem Cell Fate Reversibility and Long-Term Maintenance in the Hair Follicle","volume":"32","author":"Kim","year":"2020","journal-title":"Cell Metab."},{"key":"ref_309","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/cdd.2017.8","article-title":"Rictor\/mTORC2 deficiency enhances keratinocyte stress tolerance via mitohormesis","volume":"24","author":"Tassone","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1038\/s41467-022-28705-x","article-title":"Adaptive translational reprogramming of metabolism limits the response to targeted therapy in BRAF(V600) melanoma","volume":"13","author":"Smith","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_311","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1038\/s41571-019-0204-6","article-title":"Cell-state dynamics and therapeutic resistance in melanoma from the perspective of MITF and IFNgamma pathways","volume":"16","author":"Bai","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/s41422-019-0224-x","article-title":"Sustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade","volume":"29","author":"Jacquelot","year":"2019","journal-title":"Cell Res."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"2090","DOI":"10.1172\/JCI77746","article-title":"mTORC1 and mTORC2 selectively regulate CD8(+) T cell differentiation","volume":"125","author":"Pollizzi","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1002\/ijc.31842","article-title":"Rapalog combined with CCR4 antagonist improves anticancer vaccines efficacy","volume":"143","author":"Beziaud","year":"2018","journal-title":"Int. J. Cancer"},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1158\/2326-6066.CIR-13-0046","article-title":"mTOR inhibition improves antitumor effects of vaccination with antigen-encoding RNA","volume":"1","author":"Diken","year":"2013","journal-title":"Cancer Immunol. Res."},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1038\/bjc.2011.15","article-title":"Temsirolimus, an mTOR inhibitor, enhances anti-tumour effects of heat shock protein cancer vaccines","volume":"104","author":"Wang","year":"2011","journal-title":"Br. J. Cancer"},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.semcancer.2017.04.015","article-title":"PI3K-AKT-mTOR inhibition in cancer immunotherapy, redux","volume":"48","author":"Massi","year":"2018","journal-title":"Semin. Cancer Biol."},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"85054","DOI":"10.18632\/oncotarget.18841","article-title":"Preclinical efficacy of the novel competitive NAMPT inhibitor STF-118804 in pancreatic cancer","volume":"8","author":"Chini","year":"2017","journal-title":"Oncotarget"},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1016\/j.bbrc.2015.01.111","article-title":"FK866-induced NAMPT inhibition activates AMPK and downregulates mTOR signaling in hepatocarcinoma cells","volume":"458","author":"Schuster","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1126\/science.aau3903","article-title":"Direct stimulation of NADP(+) synthesis through Akt-mediated phosphorylation of NAD kinase","volume":"363","author":"Hoxhaj","year":"2019","journal-title":"Science"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/9985\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:21:54Z","timestamp":1760142114000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/17\/9985"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,1]]},"references-count":320,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["ijms23179985"],"URL":"https:\/\/doi.org\/10.3390\/ijms23179985","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,1]]}}}