Targeting autophagy in colorectal cancer: An update on pharmacological small-molecule compounds. Issue 8 (August 2022)

• Record Type: Journal Article
• Authors: Li, Zixiang; Si, Wen; Jin, Wenke; Yuan, Zhaoxin; Chen, Yi; Fu, Leilei
• Is Part Of: Drug discovery today. Volume 27:Issue 8(2022)
• Page Start: 2373
• Page End: 2385
• Publication Date: 2022-08
• Subjects: Autophagy -- Colorectal cancer -- Small-molecule compound -- Cytoprotective autophagy -- Autophagy-associated cell death; 5-FU 5-Fluorouracil -- AKT Protein kinase B -- AMPK AMP-activated protein kinase -- ATG6 Autophagy-related gene 6 -- BRD4 Bromodomain-containing protein 4 -- CJ Chaetocochin J -- CK2 Casein kinase 2 -- CRC Colorectal cancer -- ERK/MAPK Ras/Raf/MEK/ERK mitogen-activated protein kinase -- HDAC Histone deacetylases -- IC50 The half maximal inhibitory concentrations -- LIF Leukemia inhibitory factor -- MAPK Mitogen-activated protein kinase -- mTOR Mammalian target of rapamycin -- mTORC1 mTOR complex 1 -- OA Oleanolic acid -- PAM PI3K/AKT/mTOR -- PIK3C3 phosphoinositide 3-kinase class III -- PI3K Phosphatidylinositol-3-kinase -- SGK1 Serum/glucocorticoid-regulated kinase 1 -- STAT3 Signal transducer and activator of transcription 3 -- ULK1 Unc-51-like autophagy activating kinase 1 -- VPS34 Vacuolar protein sorting 34; Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2022.05.011
• Languages: English
• ISSNs: 1359-6446

Abstract

Graphical abstract: Highlights: Autophagy plays the Janus role in colorectal cancer (CRC). Autophagy-associated cell death and cytoprotective autophagy are involved in carcinogenesis. Small-molecule compounds modulate autophagy-associated cell death or cytoprotective autophagy in CRC. Targeting of autophagy is a potential strategy for the discovery of drugs to treat CRC. Abstract: Autophagy, an evolutionarily highly conserved cellular degradation process, plays the Janus role (either cytoprotective or death-promoting) in colorectal cancer, so the targeting of several key autophagic pathways with small-molecule compounds may be a new therapeutic strategy. In this review, we discuss autophagy-associated cell death pathways and key cytoprotective autophagy pathways in colorectal cancer. Moreover, we summarize a series of small-molecule compounds that have the potential to modulate autophagy-associated cell death or cytoprotective autophagy for therapeutic purposes. Taken together, these findings demonstrate the Janus role of autophagy in colorectal cancer, and shed new light on the exploitation of a growing number of small-molecule compounds to target autophagy in future cancer drug discovery.