{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T13:22:54Z","timestamp":1793020974665,"version":"4.5.0"},"reference-count":97,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T00:00:00Z","timestamp":1763683200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL-149303"],"award-info":[{"award-number":["HL-149303"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["AI-156921"],"award-info":[{"award-number":["AI-156921"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL-134740"],"award-info":[{"award-number":["HL-134740"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL160014"],"award-info":[{"award-number":["HL160014"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL174014"],"award-info":[{"award-number":["HL174014"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL147550"],"award-info":[{"award-number":["HL147550"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["HL160557"],"award-info":[{"award-number":["HL160557"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA 233610"],"award-info":[{"award-number":["CA 233610"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA240941"],"award-info":[{"award-number":["CA240941"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"name":"VA Merit Review","award":["I01BX001232"],"award-info":[{"award-number":["I01BX001232"]}]},{"DOI":"10.13039\/100000005","name":"U.S. Department of Defense","doi-asserted-by":"publisher","award":["HT9425-25-1-0309"],"award-info":[{"award-number":["HT9425-25-1-0309"]}],"id":[{"id":"10.13039\/100000005","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Miami Heart Research Foundation"},{"name":"National Institutes of Health Research BioMedical Research Centre at University College Hospitals London"},{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Texas MD Anderson Cancer Center Institutional Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Src homology 2-domain containing protein tyrosine phosphatase 2 (SHP2), encoded by the Ptpn11 gene (Tyrosine-protein phosphatase non-receptor type 11), is a key downstream effector of PD-1\/PD-L1 signaling and is likely important, in addition to immune modulation, in tumor development and vascular homeostasis. SHP2 conveys PD-1 mediated inhibitory signaling in T cells, and is emerging as a therapeutic target. Importantly, there is an association between immune checkpoint inhibitors (ICIs), immune-related adverse events (irAEs), and cardiovascular complications, underscoring the need to understand SHP2\u2019s role in these processes. This review aims to summarize current knowledge on SHP2\/PTPN11 biology, its role in immune regulation, cancer progression, and vascular homeostasis, and to discuss emerging therapeutic strategies targeting this pathway. The concept of using SHP2 inhibitors with immune checkpoint inhibitors (ICIs) is being investigated to address ICI resistance and to improve anti-tumor efficacy substantially. SHP2 is also being studied in non-cancer cell contexts, and signaling responses can differ by large magnitudes depending on the biological context and stimuli. Under normal circumstances, SHP2 promotes vascular homeostasis in endothelial cells (ECs) and myeloid cells and inhibits inflammation, and the reduction in SHP2 activity by oxidative stress, such as in atherosclerosis or diabetes, upregulates inflammation. In contrast, in response to radiation, the fibrotic response and subsequent lung injury were increased by endothelial SHP2 induction via Notch-Jag1 signaling. Vascular smooth muscle cells SHP2 act as a pro-atherogenic effector by enhancing ERK\/MAPK signaling, and the upregulation of mitochondria localized SHP2 can also induce cellular senescence-associated inflammation by upregulating mitochondrial reactive oxygen species. Taken together, the two opposite signaling effects of SHP2 suggest that both the immune and vascular system responses appear to be more modulated by the redox, cell, and compartment-specific signaling of SHP2. More studies are needed for mitigating cardiovascular toxicity to patients, particularly with ICI-based treatment regimens.<\/jats:p>","DOI":"10.3390\/antiox14121388","type":"journal-article","created":{"date-parts":[[2025,11,21]],"date-time":"2025-11-21T11:04:31Z","timestamp":1763723071000},"page":"1388","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9258-3016","authenticated-orcid":false,"given":"Silvia Fernanda","family":"L\u00f3pez Moreno","sequence":"first","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"},{"name":"Escuela de Medicina y Ciencias de la Salud, Instituto Tecnol\u00f3gico y de Estudios Superiores de Monterrey, Monterrey 64710, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania Assunto","family":"Lenz","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"},{"name":"Escuela de Medicina y Ciencias de la Salud, Instituto Tecnol\u00f3gico y de Estudios Superiores de Monterrey, Monterrey 64710, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3375-3724","authenticated-orcid":false,"given":"Bernardo","family":"Casso-Chapa","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"},{"name":"Escuela de Medicina y Ciencias de la Salud, Instituto Tecnol\u00f3gico y de Estudios Superiores de Monterrey, Monterrey 64710, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7539-8646","authenticated-orcid":false,"given":"Angelica","family":"Paniagua-Bojorges","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"},{"name":"Escuela de Medicina y Ciencias de la Salud, Instituto Tecnol\u00f3gico y de Estudios Superiores de Monterrey, Monterrey 64710, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8526-1315","authenticated-orcid":false,"given":"Jung Hyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"},{"name":"Escuela de Medicina y Ciencias de la Salud, Instituto Tecnol\u00f3gico y de Estudios Superiores de Monterrey, Monterrey 64710, Nuevo Le\u00f3n, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7565-1797","authenticated-orcid":false,"given":"Nicolas L.","family":"Palaskas","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9680-8298","authenticated-orcid":false,"given":"Kevin T.","family":"Nead","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venkata S. K.","family":"Samanthapudi","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilbert","family":"Mejia","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5304-585X","authenticated-orcid":false,"given":"Oanh","family":"Hoang","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1182-9653","authenticated-orcid":false,"given":"Jonghae","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"},{"name":"Department of Pediatric Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4411-0634","authenticated-orcid":false,"given":"Steven H.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joerg","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Cardio Oncology Clinic, Division of Preventive Cardiology, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN 55905, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syed Wamique","family":"Yusuf","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8817-4579","authenticated-orcid":false,"given":"Cezar A.","family":"Iliescu","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah I.","family":"Beinart","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Manisty","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Science, University College London, London WC1E 6BT, UK"},{"name":"Cardio-Oncology Department, Barts Heart Centre, Barts Health NHS Trust, London EC1A 7BE, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masuko","family":"Ushio-Fukai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiology, Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-571X","authenticated-orcid":false,"given":"Tohru","family":"Fukai","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiology, Vascular Biology Center, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7167-7287","authenticated-orcid":false,"given":"Pietro","family":"Ameri","sequence":"additional","affiliation":[{"name":"Cardiovascular Disease Unit, IRCCS Ospedale Policlinico San Martino, 16132 Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roza I.","family":"Nurieva","sequence":"additional","affiliation":[{"name":"Department of Immunology, Division of Discovery Science, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle A. T.","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Department of Lymphoma\/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1675-0514","authenticated-orcid":false,"given":"Keri","family":"Schadler","sequence":"additional","affiliation":[{"name":"Department of Pediatric Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efstratios","family":"Koutroumpakis","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivareddy","family":"Kotla","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7746-7328","authenticated-orcid":false,"given":"Nhat-Tu","family":"Le","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Sciences, Houston Methodist Research Institute, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7439-7774","authenticated-orcid":false,"given":"Jun-ichi","family":"Abe","sequence":"additional","affiliation":[{"name":"Department of Cardiology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1057, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1186\/s12943-024-02179-5","article-title":"Current trends in sensitizing immune checkpoint inhibitors for cancer treatment","volume":"23","author":"Wei","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3044","DOI":"10.3390\/curroncol29050247","article-title":"Immune Checkpoint Inhibitors in Cancer Therapy","volume":"29","author":"Shiravand","year":"2022","journal-title":"Curr. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Jo, W., Won, T., Daoud, A., and Cihakova, D. (2024). Immune checkpoint inhibitors associated cardiovascular immune-related adverse events. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1340373"},{"key":"ref_4","first-page":"10","article-title":"Newly diagnosed cardiovascular disease in patients treated with immune checkpoint inhibitors: A retrospective analysis of patients at an academic tertiary care center","volume":"7","author":"Waheed","year":"2021","journal-title":"Cardiooncology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/s41590-022-01385-x","article-title":"SHP-2 and PD-1-SHP-2 signaling regulate myeloid cell differentiation and antitumor responses","volume":"24","author":"Christofides","year":"2023","journal-title":"Nat. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Niogret, C., Birchmeier, W., and Guarda, G. (2019). SHP-2 in Lymphocytes\u2019 Cytokine and Inhibitory Receptor Signaling. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.02468"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1006\/excr.2001.5397","article-title":"Tyrosine phosphatases SHP-1 and SHP-2 are associated with distinct tyrosine-phosphorylated proteins","volume":"272","author":"Xu","year":"2002","journal-title":"Exp. Cell Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3057","DOI":"10.1046\/j.1432-1033.2002.02986.x","article-title":"Molecular mechanisms underlying SHP-1 gene expression","volume":"269","author":"Tsui","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1016\/S0968-0004(03)00091-4","article-title":"The \u2018Shp\u2019ing news: SH2 domain-containing tyrosine phosphatases in cell signaling","volume":"28","author":"Neel","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2339","DOI":"10.1158\/2159-8290.CD-23-0383","article-title":"SHP2: A Pleiotropic Target at the Interface of Cancer and Its Microenvironment","volume":"13","author":"Sodir","year":"2023","journal-title":"Cancer Discov."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tojjari, A., Saeed, A., Sadeghipour, A., Kurzrock, R., and Cavalcante, L. (2023). Overcoming Immune Checkpoint Therapy Resistance with SHP2 Inhibition in Cancer and Immune Cells: A Review of the Literature and Novel Combinatorial Approaches. Cancers, 15.","DOI":"10.3390\/cancers15225384"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"29330","DOI":"10.1074\/jbc.M112450200","article-title":"The novel role of the C-terminal region of SHP-2. Involvement of Gab1 and SHP-2 phosphatase activity in Elk-1 activation","volume":"277","author":"Huang","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1007\/s13402-022-00698-1","article-title":"A comprehensive review of SHP2 and its role in cancer","volume":"45","author":"Asmamaw","year":"2022","journal-title":"Cell Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.cellsig.2007.10.002","article-title":"The molecular functions of Shp2 in the Ras\/Mitogen-activated protein kinase (ERK1\/2) pathway","volume":"20","author":"Dance","year":"2008","journal-title":"Cell Signal."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5439","DOI":"10.1038\/s41467-022-32918-5","article-title":"Structural insights into the pSer\/pThr dependent regulation of the SHP2 tyrosine phosphatase in insulin and CD28 signaling","volume":"13","author":"Zeke","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"26908","DOI":"10.1074\/jbc.273.41.26908","article-title":"The COOH-terminal tyrosine phosphorylation sites on IRS-1 bind SHP-2 and negatively regulate insulin signaling","volume":"273","author":"Myers","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"104595","DOI":"10.1016\/j.phrs.2019.104595","article-title":"Targeting SHP2 as a promising strategy for cancer immunotherapy","volume":"152","author":"Liu","year":"2020","journal-title":"Pharmacol. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1016\/j.bbrc.2003.11.070","article-title":"Characterization of phosphotyrosine binding motifs in the cytoplasmic domain of B and T lymphocyte attenuator required for association with protein tyrosine phosphatases SHP-1 and SHP-2","volume":"312","author":"Gavrieli","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.ejmg.2015.08.005","article-title":"SHP2 sails from physiology to pathology","volume":"58","author":"Tajan","year":"2015","journal-title":"Eur. J. Med. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2075","DOI":"10.1111\/jcmm.12618","article-title":"Functions of Shp2 in cancer","volume":"19","author":"Zhang","year":"2015","journal-title":"J. Cell. Mol. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6946","DOI":"10.1074\/jbc.M608338200","article-title":"SHP-2 regulates cell growth by controlling the mTOR\/S6 kinase 1 pathway","volume":"282","author":"Zito","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1046\/j.1365-2443.2003.00615.x","article-title":"A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway","volume":"8","author":"Kimura","year":"2003","journal-title":"Genes Cells"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.jphs.2020.06.002","article-title":"Phosphatase-independent functions of SHP2 and its regulation by small molecule compounds","volume":"144","author":"Guo","year":"2020","journal-title":"J. Pharmacol. Sci."},{"key":"ref_24","first-page":"6674","article-title":"Role of SH-PTP2, a protein-tyrosine phosphatase with Src homology 2 domains, in insulin-stimulated Ras activation","volume":"14","author":"Noguchi","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1038\/aps.2010.168","article-title":"The role of Src homology 2 containing protein tyrosine phosphatase 2 in vascular smooth muscle cell migration and proliferation","volume":"31","author":"Kandadi","year":"2010","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/sj.cr.7290055","article-title":"The SHP-2 tyrosine phosphatase: Signaling mechanisms and biological functions","volume":"10","author":"Qu","year":"2000","journal-title":"Cell Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1016\/j.gde.2009.04.001","article-title":"The RASopathies: Developmental syndromes of Ras\/MAPK pathway dysregulation","volume":"19","author":"Tidyman","year":"2009","journal-title":"Curr. Opin. Genet. Dev."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"4136","DOI":"10.1021\/bi5002695","article-title":"Molecular basis of gain-of-function LEOPARD syndrome-associated SHP2 mutations","volume":"53","author":"Yu","year":"2014","journal-title":"Biochemistry"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"10472","DOI":"10.1074\/jbc.M113.450023","article-title":"Structural and mechanistic insights into LEOPARD syndrome-associated SHP2 mutations","volume":"288","author":"Yu","year":"2013","journal-title":"J. Biol. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"6018","DOI":"10.1038\/sj.onc.1204699","article-title":"The tyrosine phosphatase SHP-2 is required for mediating phosphatidylinositol 3-kinase\/Akt activation by growth factors","volume":"20","author":"Wu","year":"2001","journal-title":"Oncogene"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1002\/jcp.10446","article-title":"SHP-2 regulates the phosphatidylinositide 3\u2019-kinase\/Akt pathway and suppresses caspase 3-mediated apoptosis","volume":"199","author":"Kontaridis","year":"2004","journal-title":"J. Cell Physiol."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wei, X., Zheng, L., Tian, Y., Wang, H., Su, Y., Feng, G., Wang, C., and Lu, Z. (2022). Tyrosine phosphatase SHP2 in ovarian granulosa cells balances follicular development by inhibiting PI3K\/AKT signaling. J. Mol. Cell Biol., 14.","DOI":"10.1093\/jmcb\/mjac048"},{"key":"ref_33","first-page":"e170340","article-title":"Phase separation of SHP2E76K promotes malignant transformation of mesenchymal stem cells by activating mitochondrial complexes","volume":"9","author":"Kan","year":"2024","journal-title":"JCI Insight"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2393","DOI":"10.1007\/s00018-004-4211-z","article-title":"Tyrosine phosphatase activity in mitochondria: Presence of Shp-2 phosphatase in mitochondria","volume":"61","author":"Salvi","year":"2004","journal-title":"Cell Mol. Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1038\/s41467-017-02351-0","article-title":"Tyrosine phosphatase SHP2 negatively regulates NLRP3 inflammasome activation via ANT1-dependent mitochondrial homeostasis","volume":"8","author":"Guo","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.cell.2008.03.039","article-title":"Oncogene-induced senescence relayed by an interleukin-dependent inflammatory network","volume":"133","author":"Kuilman","year":"2008","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1016\/j.cmet.2016.05.010","article-title":"From Ancient Pathways to Aging Cells-Connecting Metabolism and Cellular Senescence","volume":"23","author":"Wiley","year":"2016","journal-title":"Cell Metab."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1126\/science.aaf6659","article-title":"Senescent intimal foam cells are deleterious at all stages of atherosclerosis","volume":"354","author":"Childs","year":"2016","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1161\/CIRCULATIONAHA.115.016457","article-title":"Vascular Smooth Muscle Cell Senescence Promotes Atherosclerosis and Features of Plaque Vulnerability","volume":"132","author":"Wang","year":"2015","journal-title":"Circulation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1007\/s10522-024-10114-w","article-title":"Inhibitory immune checkpoints suppress the surveillance of senescent cells promoting their accumulation with aging and in age-related diseases","volume":"25","author":"Salminen","year":"2024","journal-title":"Biogerontology"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Wang, Y., Mohseni, M., Grauel, A., Diez, J.E., Guan, W., Liang, S., Choi, J.E., Pu, M., Chen, D., and Laszewski, T. (2021). SHP2 blockade enhances anti-tumor immunity via tumor cell intrinsic and extrinsic mechanisms. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-80999-x"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.15252\/embj.201489004","article-title":"Shp2 signaling suppresses senescence in PyMT-induced mammary gland cancer in mice","volume":"34","author":"Lan","year":"2015","journal-title":"EMBO J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.semcdb.2014.09.013","article-title":"The role of the protein tyrosine phosphatase SHP2 in cardiac development and disease","volume":"37","author":"Lauriol","year":"2015","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"8816","DOI":"10.1158\/0008-5472.CAN-04-1923","article-title":"Activating mutations of the noonan syndrome-associated SHP2\/PTPN11 gene in human solid tumors and adult acute myelogenous leukemia","volume":"64","author":"Paez","year":"2004","journal-title":"Cancer Res."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Xu, D., Zheng, H., Yu, W.M., and Qu, C.K. (2013). Activating mutations in protein tyrosine phosphatase Ptpn11 (Shp2) enhance reactive oxygen species production that contributes to myeloproliferative disorder. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063152"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4257","DOI":"10.1073\/pnas.1119803109","article-title":"Noonan syndrome-causing SHP2 mutants inhibit insulin-like growth factor 1 release via growth hormone-induced ERK hyperactivation, which contributes to short stature","volume":"109","author":"Edouard","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1717","DOI":"10.1093\/carcin\/bgu025","article-title":"SHP2E76K mutant promotes lung tumorigenesis in transgenic mice","volume":"35","author":"Schneeberger","year":"2014","journal-title":"Carcinogenesis"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1237","DOI":"10.1158\/2159-8290.CD-18-0444","article-title":"SHP2 Inhibition Prevents Adaptive Resistance to MEK Inhibitors in Multiple Cancer Models","volume":"8","author":"Fedele","year":"2018","journal-title":"Cancer Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/ni1443","article-title":"The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection","volume":"8","author":"Sharpe","year":"2007","journal-title":"Nat. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1038\/s41422-020-0343-4","article-title":"Immune checkpoint signaling and cancer immunotherapy","volume":"30","author":"He","year":"2020","journal-title":"Cell Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/s12943-024-02023-w","article-title":"Regulatory mechanisms of PD-1\/PD-L1 in cancers","volume":"23","author":"Lin","year":"2024","journal-title":"Mol. Cancer"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"eaay4458","DOI":"10.1126\/sciadv.aay4458","article-title":"Molecular mechanism of SHP2 activation by PD-1 stimulation","volume":"6","author":"Marasco","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.molcel.2019.12.012","article-title":"PD-1 Imposes Qualitative Control of Cellular Transcriptomes in Response to T Cell Activation","volume":"77","author":"Shimizu","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"6310","DOI":"10.1038\/s41467-021-26697-8","article-title":"Endothelial deletion of SHP2 suppresses tumor angiogenesis and promotes vascular normalization","volume":"12","author":"Xu","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1074\/jbc.M114.614057","article-title":"Protein-tyrosine phosphatase Shp2 positively regulates macrophage oxidative burst","volume":"290","author":"Li","year":"2015","journal-title":"J. Biol. Chem."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.jaci.2022.06.021","article-title":"Allosteric inhibition of SHP2 rescues functional T-cell abnormalities in SAP deficiency","volume":"150","author":"Panchal","year":"2022","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1201","DOI":"10.1084\/jem.20112741","article-title":"Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2","volume":"209","author":"Yokosuka","year":"2012","journal-title":"J. Exp. Med."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.celrep.2018.03.026","article-title":"Shp-2 Is Dispensable for Establishing T Cell Exhaustion and for PD-1 Signaling In Vivo","volume":"23","author":"Rota","year":"2018","journal-title":"Cell Rep."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Cammann, C., Israel, N., Frentzel, S., Jeron, A., Topfstedt, E., Schuler, T., Simeoni, L., Zenker, M., Fehling, H.J., and Schraven, B. (2022). T cell-specific constitutive active SHP2 enhances T cell memory formation and reduces T cell activation. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.958616"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e2427254122","DOI":"10.1073\/pnas.2427254122","article-title":"T lymphocyte-specific deletion of SHP1 and SHP2 promotes activation-induced cell death of CD4(+) T cells and impairs antitumor response","volume":"122","author":"Foster","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1016\/j.apsb.2018.08.009","article-title":"SHP2 inhibition triggers anti-tumor immunity and synergizes with PD-1 blockade","volume":"9","author":"Zhao","year":"2019","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1016\/j.immuni.2014.06.010","article-title":"Tumor-associated macrophages: From mechanisms to therapy","volume":"41","author":"Noy","year":"2014","journal-title":"Immunity"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e162870","DOI":"10.1172\/JCI162870","article-title":"SHP2 deneddylation mediates tumor immunosuppression in colon cancer via the CD47\/SIRPalpha axis","volume":"133","author":"Li","year":"2023","journal-title":"J. Clin. Investig."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1042\/BST20150245","article-title":"Role of the colony-stimulating factor (CSF)\/CSF-1 receptor axis in cancer","volume":"44","author":"Achkova","year":"2016","journal-title":"Biochem. Soc. Trans."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.it.2017.12.005","article-title":"SIRPalpha-CD47 Immune Checkpoint Blockade in Anticancer Therapy","volume":"39","author":"Veillette","year":"2018","journal-title":"Trends Immunol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2512645","DOI":"10.1080\/21645515.2025.2512645","article-title":"A review of immune checkpoint inhibitor-associated myocarditis: Epidemiology, pathogenesis, and biomarkers","volume":"21","author":"Xu","year":"2025","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1126\/science.291.5502.319","article-title":"Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice","volume":"291","author":"Nishimura","year":"2001","journal-title":"Science"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e013757","DOI":"10.1161\/JAHA.119.013757","article-title":"Immune Checkpoint Inhibitor Myocarditis: Pathophysiological Characteristics, Diagnosis, and Treatment","volume":"9","author":"Palaskas","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1093\/jjco\/hyx154","article-title":"Immune checkpoint inhibitor-related myocarditis","volume":"48","author":"Tajiri","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/nm955","article-title":"Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice","volume":"9","author":"Okazaki","year":"2003","journal-title":"Nat. Med."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"2513","DOI":"10.4049\/jimmunol.181.4.2513","article-title":"Programmed death ligand 1 regulates a critical checkpoint for autoimmune myocarditis and pneumonitis in MRL mice","volume":"181","author":"Lucas","year":"2008","journal-title":"J. Immunol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2974","DOI":"10.1172\/JCI31344","article-title":"Proatherogenic immune responses are regulated by the PD-1\/PD-L pathway in mice","volume":"117","author":"Gotsman","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1161\/ATVBAHA.111.224709","article-title":"Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation","volume":"31","author":"Bu","year":"2011","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1016\/j.jaccao.2020.08.007","article-title":"Immune Checkpoint Inhibitor Therapy Aggravates T Cell-Driven Plaque Inflammation in Atherosclerosis","volume":"2","author":"Poels","year":"2020","journal-title":"JACC Cardio Oncol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.jacc.2021.11.048","article-title":"Immune Checkpoint Therapies and Atherosclerosis: Mechanisms and Clinical Implications: JACC State-of-the-Art Review","volume":"79","author":"Vuong","year":"2022","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s44161-023-00218-w","article-title":"Pairing of single-cell RNA analysis and T cell antigen receptor profiling indicates breakdown of T cell tolerance checkpoints in atherosclerosis","volume":"2","author":"Wang","year":"2023","journal-title":"Nat. Cardiovasc. Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1161\/ATVBAHA.123.319663","article-title":"Protein Tyrosine Phosphatase SHP2 in Macrophages Acts as an Antiatherosclerotic Regulator in Mice","volume":"44","author":"Wu","year":"2024","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4759","DOI":"10.1096\/fj.201700280R","article-title":"Endothelial cell SHP-2 negatively regulates neutrophil adhesion and promotes transmigration by enhancing ICAM-1-VE-cadherin interaction","volume":"31","author":"Yan","year":"2017","journal-title":"FASEB J."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1124","DOI":"10.1096\/fj.201800284R","article-title":"SHP2 protects endothelial cell barrier through suppressing VE-cadherin internalization regulated by MET-ARF1","volume":"33","author":"Zhang","year":"2019","journal-title":"FASEB J."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1089\/ars.2008.2027","article-title":"Redox control of endothelial function and dysfunction: Molecular mechanisms and therapeutic opportunities","volume":"10","author":"Thomas","year":"2008","journal-title":"Antioxid. Redox. Signal."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Pichavaram, P., Mani, A.M., Singh, N.K., and Rao, G.N. (2019). Cholesterol crystals promote endothelial cell and monocyte interactions via H(2)O(2)-mediated PP2A inhibition, NFkappaB activation and ICAM1 and VCAM1 expression. Redox. Biol., 24.","DOI":"10.1016\/j.redox.2019.101180"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Didion, S.P. (2017). Cellular and Oxidative Mechanisms Associated with Interleukin-6 Signaling in the Vasculature. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122563"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"103867","DOI":"10.1016\/j.isci.2022.103867","article-title":"Endothelial Shp2 deficiency controls alternative activation of macrophage preventing radiation-induced lung injury through notch signaling","volume":"25","author":"Liu","year":"2022","journal-title":"iScience"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Chen, J., Cao, Z., and Guan, J. (2018). SHP2 inhibitor PHPS1 protects against atherosclerosis by inhibiting smooth muscle cell proliferation. BMC Cardiovasc. Disord., 18.","DOI":"10.1186\/s12872-018-0816-2"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Mattoon, D.R., Lamothe, B., Lax, I., and Schlessinger, J. (2004). The docking protein Gab1 is the primary mediator of EGF-stimulated activation of the PI-3K\/Akt cell survival pathway. BMC Biol., 2.","DOI":"10.1186\/1741-7007-2-24"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.cardiores.2006.04.015","article-title":"Redox signaling in angiogenesis: Role of NADPH oxidase","volume":"71","year":"2006","journal-title":"Cardiovasc. Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1038\/s41591-018-0024-8","article-title":"Mutant KRAS-driven cancers depend on PTPN11\/SHP2 phosphatase","volume":"24","author":"Ruess","year":"2018","journal-title":"Nat. Med."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Richards, C.E., Elamin, Y.Y., Carr, A., Gately, K., Rafee, S., Cremona, M., Hanrahan, E., Smyth, R., Ryan, D., and Morgan, R.K. (2023). Protein Tyrosine Phosphatase Non-Receptor 11 (PTPN11\/Shp2) as a Driver Oncogene and a Novel Therapeutic Target in Non-Small Cell Lung Cancer (NSCLC). Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241310545"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1111\/j.1365-2559.2008.03103.x","article-title":"SHP2 is up-regulated in breast cancer cells and in infiltrating ductal carcinoma of the breast, implying its involvement in breast oncogenesis","volume":"53","author":"Zhou","year":"2008","journal-title":"Histopathology"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1038\/ng1156","article-title":"Somatic mutations in PTPN11 in juvenile myelomonocytic leukemia, myelodysplastic syndromes and acute myeloid leukemia","volume":"34","author":"Tartaglia","year":"2003","journal-title":"Nat. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"4840","DOI":"10.1158\/0008-5472.CAN-20-1634","article-title":"Allosteric SHP2 Inhibitor, IACS-13909, Overcomes EGFR-Dependent and EGFR-Independent Resistance Mechanisms toward Osimertinib","volume":"80","author":"Sun","year":"2020","journal-title":"Cancer Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1158\/1535-7163.MCT-20-0965","article-title":"SHP2 Inhibition Enhances the Effects of Tyrosine Kinase Inhibitors in Preclinical Models of Treatment-naive ALK-, ROS1-, or EGFR-altered Non-small Cell Lung Cancer","volume":"20","author":"Kano","year":"2021","journal-title":"Mol. Cancer Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"2889","DOI":"10.1158\/0008-5472.CAN-19-3038","article-title":"Allosteric Inhibition of SHP2 Stimulates Antitumor Immunity by Transforming the Immunosuppressive Environment","volume":"80","author":"Quintana","year":"2020","journal-title":"Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1021\/bi801973z","article-title":"Redox regulation of SH2-domain-containing protein tyrosine phosphatases by two backdoor cysteines","volume":"48","author":"Chen","year":"2009","journal-title":"Biochemistry"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12964-022-00906-3","article-title":"An update of Nrf2 activators and inhibitors in cancer prevention\/promotion","volume":"20","author":"Pouremamali","year":"2022","journal-title":"Cell Commun. Signal."},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Syahputra, E.W., Lee, H., Cho, H., Park, H.J., Park, K.S., and Hwang, D. (2025). PROTAC Delivery Strategies for Overcoming Physicochemical Properties and Physiological Barriers in Targeted Protein Degradation. Pharmaceutics, 17.","DOI":"10.3390\/pharmaceutics17040501"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Fallatah, M.M., Alradwan, I., Alfayez, N., Aodah, A.H., Alkhrayef, M., Majrashi, M., and Jamous, Y.F. (2025). Nanoparticles for Cancer Immunotherapy: Innovations and Challenges. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081086"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/12\/1388\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T05:23:05Z","timestamp":1763875385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/14\/12\/1388"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,21]]},"references-count":97,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["antiox14121388"],"URL":"https:\/\/doi.org\/10.3390\/antiox14121388","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,21]]}}}