Metabolic axis of autophagy: A key player in tumor maintenance and opportunities for therapeutic exploitation

Table 1 List of preclinical/clinical studies on use of autophagy inhibitors as monotherapeutic agent and their mechanism of action in human cancer types

Cancer type(s)	Pre-clinical/clinical phase	Trial identifier
Melanoma (stage III/IV)	0 (pilot study)	NCT00962845
Renal cell carcinoma	I	NCT01144169
Chronic lymphocytic leukemia	II	NCT00771056
Metastatic pancreatic adenocarcinoma	II	NCT01273805
Breast ductal carcinoma in situ	I/II	NCT01023477
Brain metastases with whole brain radiation therapy	II	NCT01894633
DCC-3116 (ULK1 inhibitor): Targets ULK1 and blocks early autophagy initiation
Kras-mutated or Raf-mutated advanced solid tumors	I (first in human)	NCT04892017
SBI-0206965 (ULK1 inhibitor): Targets ULK1 kinase and inhibits early phase autophagy initiation
Non-small cell lung cancer cells, neuroblastoma	Preclinical studies on cell lines and mouse models	Not available
Verteporfin (photoactivatable autophagy inhibitor): Inhibits autophagosome formation and lysosomal degradation
Glioblastoma, pancreatic ductal adenocarcinomas	I/II	NCT03033225
3-Methyladenine: Targets class III phosphatidylinositol 3-kinase (vacuolar protein sorting 34), thereby blocks autophagosome formation (early-stage autophagy)
Cervical cancer, breast cancer, glioblastoma, hepatocellular carcinoma, colon cancer, ovarian cancer, pancreatic cancer, leukemia, mantle cell lymphoma	Preclinical studies on cell lines and murine models	Not available
Lys05 (lysosome deacidifier): Late-stage autophagy inhibitor
Glioblastoma, colorectal cancer, melanoma, acute myeloid leukemia	Preclinical studies on cell lines and murine models	Not available

ULK: Unc-51 like autophagy activating kinase.