{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:43:02Z","timestamp":1793313782823,"version":"4.5.0"},"reference-count":80,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,5]],"date-time":"2022-03-05T00:00:00Z","timestamp":1646438400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>Autophagy has been of novel interest since it was first demonstrated to have effect in Burkitt\u2019s lymphoma. Since that time, the autophagy agents chloroquine and hydroxychloroquine have become the only FDA (Food and Drug Administration)-approved autophagy inhibitors. While not approved for cancer therapy, there are ongoing clinical trials to evaluate their safety and efficacy. Pevonedistat has emerged as a novel inhibitor through the neddylation pathway and is an autophagy activator. This paper summarizes and presents current clinical trials for hydroxychloroquine (HCQ), chloroquine (CQ), and Pevonedistat for the clinician.<\/jats:p>","DOI":"10.3390\/curroncol29030141","type":"journal-article","created":{"date-parts":[[2022,3,6]],"date-time":"2022-03-06T20:35:50Z","timestamp":1646598950000},"page":"1695-1708","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["Autophagy Agents in Clinical Trials for Cancer Therapy: A Brief Review"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9702-6714","authenticated-orcid":false,"given":"Samiha","family":"Mohsen","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Toronto, Toronto, ON M5S 1A8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9711-604X","authenticated-orcid":false,"given":"Philip T.","family":"Sobash","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, White River Health System, Batesville, AR 72501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghada Fahad","family":"Algwaiz","sequence":"additional","affiliation":[{"name":"Department of Medicine, King Faisal Specialist Hospital and Research Center, Al Mathar Ash Shamali, Riyadh 11564, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor","family":"Nasef","sequence":"additional","affiliation":[{"name":"College of Arts and Sciences, The Ohio State University, Columbus, OH 72501, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safaa Abed","family":"Al-Zeidaneen","sequence":"additional","affiliation":[{"name":"Department of Allied Medical Science, Al-Balqa\u2019 Applied University, As-Salt 2PF8+XM, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagla Abdel","family":"Karim","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Medical College of Georgia, Augusta, GA 30912, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1083\/jcb.33.2.437","article-title":"Influence of glucagon, an inducer of cellular autophagy, on some physical properties of rat liver lysosomes","volume":"33","author":"Deter","year":"1967","journal-title":"J. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"(2010). Focusing on autophagy. Nat. Cell Biol., 12, 813.","DOI":"10.1038\/ncb0910-813"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Deretic, V. (2008). Autophagosome and Phagosome. Autophagosome and Phagosome, Humana Press.","DOI":"10.1007\/978-1-59745-157-4"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Dunn, W.A. (1994). Autophagy and Related Mechanisms of Lysosome-Mediated Protein Degradation, Elsevier Ltd.","DOI":"10.1016\/0962-8924(94)90069-8"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/ncb2979","article-title":"Cargo recognition and trafficking in selective autophagy","volume":"16","author":"Stolz","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.ceb.2010.10.009","article-title":"Chaperone-mediated autophagy in protein quality control","volume":"23","author":"Arias","year":"2011","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/ni.2524","article-title":"Plasma cells require autophagy for sustainable immunoglobulin production","volume":"14","author":"Pengo","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e838","DOI":"10.1038\/cddis.2013.350","article-title":"Autophagy and chemotherapy resistance: A promising therapeutic target for cancer treatment","volume":"4","author":"Sui","year":"2013","journal-title":"Cell Death Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"7888","DOI":"10.1016\/j.bmc.2008.07.076","article-title":"The efficacy and selectivity of tumor cell killing by akt inhibitors are substantially increased by chloroquine","volume":"16","author":"Hu","year":"2008","journal-title":"Bioorganic Med. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.18632\/oncotarget.2462","article-title":"Biomolecular characterization of exosomes released from cancer stem cells: Possible implications for biomarker and treatment of cancer","volume":"6","author":"Kumar","year":"2015","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1083\/jcb.201211138","article-title":"Extracellular vesicles: Exosomes, microvesicles, and friends","volume":"200","author":"Raposo","year":"2013","journal-title":"J. Cell Biol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Sharifi, M.N., Mowers, E.E., Drake, L.E., and Macleod, K.F. (2015). Measuring Autophagy in Stressed Cells, Springer.","DOI":"10.1007\/978-1-4939-2522-3_10"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"673","DOI":"10.4161\/auto.7.7.14733","article-title":"Microautophagy in mammalian cells: Revisiting a 40-year-old conundrum","volume":"7","author":"Mijaljica","year":"2011","journal-title":"Autophagy"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1093\/oxfordjournals.aje.a115189","article-title":"Effect of a malaria suppression program on the incidence of african burkitt\u2019s lymphoma","volume":"129","author":"Geser","year":"1989","journal-title":"Am. J. Epidemiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.biochi.2014.10.001","article-title":"Inhibition of autophagy by chloroquine potentiates synergistically anti-cancer property of artemisinin by promoting ROS dependent apoptosis","volume":"107","author":"Ganguli","year":"2014","journal-title":"Biochimie"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion","volume":"14","author":"Mauthe","year":"2018","journal-title":"Autophagy"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"M\u00fcnz, C. (2016). Autophagy Beyond Intracellular MHC Class II Antigen Presentation, Elsevier.","DOI":"10.1016\/j.it.2016.08.017"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1038\/ni.3273","article-title":"Autophagy and autophagy-related proteins in the immune system","volume":"16","author":"Shibutani","year":"2015","journal-title":"Nat. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1111\/cmi.12043","article-title":"Autophagy in antiviral innate immunity","volume":"15","author":"Richetta","year":"2012","journal-title":"Cell. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3389\/fonc.2016.00246","article-title":"Hijacker of the antitumor immune response: Autophagy is showing its worst facet","volume":"6","author":"Viry","year":"2016","journal-title":"Front. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Paquette, M., El-Houjeiri, L., and Pause, A. (2018). mTOR pathways in cancer and autophagy. Cancers, 10.","DOI":"10.3390\/cancers10010018"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.tips.2012.01.005","article-title":"Hypoxia-inducible factors: Mediators of cancer progression and targets for cancer therapy","volume":"33","author":"Semenza","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/2045-3701-4-10","article-title":"Suppression of autophagy by chloroquine sensitizes 5-fluorouracil-mediated cell death in gallbladder carcinoma cells","volume":"4","author":"Liang","year":"2014","journal-title":"Cell Biosci."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.ceb.2009.03.007","article-title":"Exosomes\u2014vesicular carriers for intercellular communication","volume":"21","author":"Simons","year":"2009","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"122","DOI":"10.4161\/auto.2.2.2350","article-title":"Multivesicular bodies and autophagy in erythrocyte maturation","volume":"2","author":"Fader","year":"2006","journal-title":"Autophagy"},{"key":"ref_26","first-page":"3668","article-title":"Cisplatin-induced autophagy protects breast cancer cells from apoptosis by regulating yes-associated protein","volume":"38","author":"Jiang","year":"2017","journal-title":"Oncol. Rep."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1038\/nature04723","article-title":"Loss of autophagy in the central nervous system causes neurodegeneration in mice","volume":"441","author":"Komatsu","year":"2006","journal-title":"Nature"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"28","DOI":"10.4161\/auto.3269","article-title":"Role of autophagy in cancer: Management of metabolic stress","volume":"3","author":"Jin","year":"2007","journal-title":"Autophagy"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"15099","DOI":"10.1038\/s41598-019-51537-7","article-title":"Drug-induced PD-L1 expression and cell stress response in breast cancer cells can be balanced by drug combination","volume":"9","author":"Gilad","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1124\/mol.114.091850","article-title":"Autophagy and cancer therapy","volume":"85","author":"Thorburn","year":"2014","journal-title":"Mol. Pharmacol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1080\/15548627.2016.1260808","article-title":"Autophagic homeostasis is required for the pluripotency of cancer stem cells","volume":"13","author":"Sharif","year":"2017","journal-title":"Autophagy"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1186\/s13578-021-00570-z","article-title":"Is targeting autophagy mechanism in cancer a good approach? the possible double-edge sword effect","volume":"11","author":"Lim","year":"2021","journal-title":"Cell Biosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1186\/s12943-019-0979-1","article-title":"Neddylation: A novel modulator of the tumor microenvironment","volume":"18","author":"Zhou","year":"2019","journal-title":"Molecular cancer Mol. Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1177\/1947601910382898","article-title":"The NEDD8 conjugation pathway and its relevance in cancer biology and therapy","volume":"1","author":"Soucy","year":"2010","journal-title":"Genes Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e29911","DOI":"10.4161\/mco.29911","article-title":"Chloroquine and hydroxychloroquine for cancer therapy","volume":"1","author":"Manic","year":"2014","journal-title":"Mol. Cell. Oncol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1146\/annurev-cancerbio-041816-122338","article-title":"The role of autophagy in cancer","volume":"1","author":"Mancias","year":"2017","journal-title":"Annu. Rev. Cancer Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Chude, C.I., and Amaravadi, R.K. (2017). Targeting autophagy in cancer: Update on clinical trials and novel inhibitors. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18061279"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s10549-019-05381-y","article-title":"A randomized, double-blind, window of opportunity trial evaluating the effects of chloroquine in breast cancer patients","volume":"178","author":"Arnaout","year":"2019","journal-title":"Breast Cancer Res. Treat."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.clbc.2020.09.015","article-title":"A phase II study of the efficacy and safety of chloroquine in combination with taxanes in the treatment of patients with advanced or metastatic anthracycline-refractory breast cancer","volume":"21","author":"Anand","year":"2021","journal-title":"Clin. Breast Cancer"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3027","DOI":"10.1200\/JCO.2019.37.15_suppl.3027","article-title":"Phase I trial of chloroquine (CQ)\/hydroxychloroquine (HCQ) in combination with carboplatin-gemcitabine (CG) in patients with advanced solid tumors","volume":"37","author":"Ahmad","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1007\/s00280-017-3446-y","article-title":"Phase I study of a chloroquine\u2013gemcitabine combination in patients with metastatic or unresectable pancreatic cancer","volume":"80","author":"Samaras","year":"2017","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_42","first-page":"CT140","article-title":"Abstract CT140: PINC trial: Preventing invasive breast neoplasia with chloroquine","volume":"77","author":"Espina","year":"2017","journal-title":"Clinical Trials"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Khurshed, M., Molenaar, R., van Linde, M., Math\u00f4t, R., Struys, E., van Wezel, T., van Noorden, C., Kl\u00fcmpen, H.-J., Bov\u00e9e, J., and Wilmink, J. (2021). A phase ib clinical trial of metformin and chloroquine in patients with idh1-mutated solid tumors. Cancers, 13.","DOI":"10.3390\/cancers13102474"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s13566-013-0111-x","article-title":"Concurrent whole brain radiotherapy and short-course chloroquine in patients with brain metastases: A pilot trial","volume":"2","author":"Eldredge","year":"2013","journal-title":"J. Radiat. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"5775","DOI":"10.1182\/blood.V124.21.5775.5775","article-title":"A phase II trial of chloroquine in combination with bortezomib and cyclophosphamide in patients with relapsed and refractory multiple myeloma","volume":"124","author":"Montanari","year":"2014","journal-title":"Blood"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"v154","DOI":"10.1093\/annonc\/mdz243.035","article-title":"CHLOROBRAIN phase IB trial: The addition of chloroquine, an autophagy inhibitor, to concurrent radiation and temozolomide for newly diagnosed glioblastoma","volume":"30","author":"Compter","year":"2019","journal-title":"Ann. Oncol."},{"key":"ref_47","first-page":"1","article-title":"Therapy of glioblastoma multiforme improved by the antimutagenic chloroquine","volume":"14","author":"Reyes","year":"2003","journal-title":"Neurosurg. Focus"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1634\/theoncologist.2014-0086","article-title":"Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma","volume":"19","author":"Wolpin","year":"2014","journal-title":"Oncologist"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"100158","DOI":"10.1016\/j.ctarc.2019.100158","article-title":"Phase ib\/II study of hydroxychloroquine in combination with chemotherapy in patients with metastatic non-small cell lung cancer (NSCLC)","volume":"21","author":"Malhotra","year":"2019","journal-title":"Cancer Treat. Res. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3551","DOI":"10.1200\/JCO.2019.37.15_suppl.3551","article-title":"Modulation of autophagy: A phase II study of vorinostat (VOR) plus hydroxychloroquine (HCQ) vs. regorafenib (RGF) in chemo-refractory metastatic colorectal cancer (mCRC)","volume":"37","author":"Arora","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"e15580","DOI":"10.1200\/JCO.2021.39.15_suppl.e15580","article-title":"Phase I trial of regorafenib, hydroxychloroquine, and entinostat in metastatic colorectal cancer","volume":"39","author":"Brown","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e21138","DOI":"10.1200\/JCO.2018.36.15_suppl.e21138","article-title":"Modulation of autophagy with hydroxychloroquine in patients with advanced non-small cell lung cancer (NSCLC): A phase ib study","volume":"36","author":"Malhotra","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"190","DOI":"10.18632\/genesandcancer.181","article-title":"Neoadjuvant administration of hydroxychloroquine in a phase 1 clinical trial induced plasma par-4 levels and apoptosis in diverse tumors","volume":"9","author":"Wang","year":"2018","journal-title":"Genes Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.4161\/auto.29118","article-title":"Phase I trial of hydroxychloroquine with dose-intense temozolomide in patients with advanced solid tumors and melanoma","volume":"10","author":"Rangwala","year":"2014","journal-title":"Autophagy"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3614","DOI":"10.1200\/jco.2015.33.15_suppl.3614","article-title":"Phase II trial of autophagy inhibition using hydroxychloroquine (HCQ) with FOLFOX\/bevacizumab in the first-line treatment of advanced colorectal cancer","volume":"33","author":"Redlinger","year":"2015","journal-title":"J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"4402","DOI":"10.1245\/s10434-015-4566-4","article-title":"Safety and Biologic Response of Pre-Operative Autophagy Inhibition with Gemcitabine in Patients with Pancreatic Adenocarcinoma","volume":"22","author":"Boone","year":"2015","journal-title":"Ann. Surg. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1001\/jamaoncol.2019.0684","article-title":"Effect of gemcitabine and nab-paclitaxel with or without hydroxychloroquine on patients with advanced pancreatic cancer: A phase 2 randomized clinical trial","volume":"5","author":"Karasic","year":"2019","journal-title":"JAMA Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1097\/JTO.0b013e318262de4a","article-title":"A phase I study of erlotinib and hydroxychloroquine in advanced Non\u2013Small-cell lung cancer","volume":"7","author":"Goldberg","year":"2012","journal-title":"J. Thorac. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.4161\/auto.28984","article-title":"A phase I\/II trial of hydroxychloroquine in conjunction with radiation therapy and concurrent and adjuvant temozolomide in patients with newly diagnosed glioblastoma multiforme","volume":"10","author":"Rosenfeld","year":"2014","journal-title":"Autophagy"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1869","DOI":"10.1182\/blood.V118.21.1869.1869","article-title":"Combined autophagy and proteasome inhibition for multiple myeloma: Final results of a phase 1 trial of hydroxychloroquine and standard dose bortezomib for patients with relapsed or refractory myeloma","volume":"118","author":"Vogl","year":"2011","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1182\/blood.V124.21.3449.3449","article-title":"A phase I study of hydroxychloroquine with infusional cyclophosphamide, pulse dexamethasone and rapamycin in patients with relapsed or refractory multiple myeloma","volume":"124","author":"Scott","year":"2014","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1200\/JCO.2018.36.15_suppl.4573","article-title":"Safety and activity of hydroxychloroquine and aldesleukin in metastatic renal cell carcinoma: A cytokine working group phase II study","volume":"36","author":"Appleman","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1016\/j.chest.2017.01.033","article-title":"Sirolimus and autophagy inhibition in lymphangioleiomyomatosis: Results of a phase I clinical trial","volume":"151","author":"Goldberg","year":"2017","journal-title":"Chest"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1158\/1078-0432.CCR-18-2204","article-title":"Autophagy inhibition to augment mTOR inhibition: A phase I\/II trial of everolimus and hydroxychloroquine in patients with previously treated renal cell carcinoma","volume":"25","author":"Haas","year":"2019","journal-title":"Clin. Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1158\/1078-0432.CCR-19-4042","article-title":"A randomized phase II preoperative study of autophagy inhibition with high-dose hydroxychloroquine and gemcitabine\/nab-paclitaxel in pancreatic cancer patients","volume":"26","author":"Zeh","year":"2020","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10637-018-0610-0","article-title":"Phase ib study of pevonedistat, a NEDD8-activating enzyme inhibitor, in combination with docetaxel, carboplatin and paclitaxel, or gemcitabine, in patients with advanced solid tumors","volume":"37","author":"Lockhart","year":"2019","journal-title":"Investig. New Drugs"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1007\/s10637-020-01017-x","article-title":"Phase I study assessing the mass balance, pharmacokinetics, and excretion of [ 14 C]-pevonedistat, a NEDD8-activating enzyme inhibitor in patients with advanced solid tumors","volume":"39","author":"Zhou","year":"2021","journal-title":"Investig. New Drugs"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1182\/blood-2017-09-805895","article-title":"Pevonedistat, a first-in-class NEDD8-activating enzyme inhibitor, combined with azacitidine in patients with AML","volume":"131","author":"Swords","year":"2018","journal-title":"Blood"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"8529","DOI":"10.1200\/jco.2011.29.15_suppl.8529","article-title":"MLN4924, an investigational NEDD8-activating enzyme (NAE) inhibitor, in patients (pts) with metastatic melanoma: Results of a phase I study","volume":"29","author":"Bhatia","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1038\/s41375-021-01125-4","article-title":"Randomized phase 2 trial of pevonedistat plus azacitidine versus azacitidine for higher-risk MDS\/CMML or low-blast AML","volume":"35","author":"Sekeres","year":"2021","journal-title":"Leukemia"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"534","DOI":"10.1111\/bjh.13323","article-title":"Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: A phase 1 study","volume":"169","author":"Swords","year":"2015","journal-title":"Br. J. Haematol."},{"key":"ref_72","first-page":"1","article-title":"Autophagy modulation in cancer: Current knowledge on action and therapy","volume":"2018","author":"Buljubasic","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"659","DOI":"10.4161\/auto.6058","article-title":"Autophagy upregulation by inhibitors of caspase-3 and mTOR enhances radiotherapy in a mouse model of lung cancer","volume":"4","author":"Kim","year":"2008","journal-title":"Autophagy"},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Xie, X., White, E.P., and Mehnert, J.M. (2013). Coordinate autophagy and mTOR pathway inhibition enhances cell death in melanoma. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0055096"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nrd3802","article-title":"Autophagy modulation as a potential therapeutic target for diverse diseases. Nature reviews","volume":"11","author":"Rubinsztein","year":"2012","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"627639","DOI":"10.3389\/fcell.2021.627639","article-title":"Overcoming chemoresistance: Altering pH of cellular compartments by chloroquine and hydroxychloroquine","volume":"9","author":"Halcrow","year":"2021","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"562","DOI":"10.4161\/auto.27901","article-title":"Acidic extracellular pH neutralizes the autophagy-inhibiting activity of chloroquine","volume":"10","author":"Pellegrini","year":"2014","journal-title":"Autophagy"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1111\/imm.13160","article-title":"Dissecting pharmacological effects of chloroquine in cancer treatment: Interference with inflammatory signaling pathways","volume":"159","author":"Varisli","year":"2020","journal-title":"Immunology"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"101990","DOI":"10.1016\/j.isci.2020.101990","article-title":"Hydroxychloroquine can impair tumor response to anti-PD1 in subcutaneous mouse models","volume":"24","author":"Wabitsch","year":"2021","journal-title":"iScience"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13578-020-00396-1","article-title":"mTOR signaling pathway and mTOR inhibitors in cancer: Progress and challenges","volume":"10","author":"Zou","year":"2020","journal-title":"Cell Biosci."}],"container-title":["Current Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/3\/141\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:32:42Z","timestamp":1760135562000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1718-7729\/29\/3\/141"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,5]]},"references-count":80,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["curroncol29030141"],"URL":"https:\/\/doi.org\/10.3390\/curroncol29030141","relation":{},"ISSN":["1718-7729"],"issn-type":[{"value":"1718-7729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,5]]}}}