Recent advances in targeting autophagy in cancer

• Published in: Trends in pharmacological sciences (Regular ed.) 2023-05, Vol.44 (5), p.290-302
• Main Authors: Jain, Vaibhav, Singh, Mahendra Pal, Amaravadi, Ravi K.
• Format: Article
• Language: English
• Subjects: Autophagy; cancer; Humans; hydroxychloroquine; Hydroxychloroquine - pharmacology; Hydroxychloroquine - therapeutic use; immunotherapy, chemotherapy; lysosome; Neoplasms - drug therapy; Neoplasms - pathology
• ISSN: 0165-6147; 1873-3735
• DOI: 10.1016/j.tips.2023.02.003

Autophagy is a degradative and recycling process that is upregulated in cancer cells.New advances in understanding the mechanism of autophagy have uncovered novel potential targets for drug development.Clinical trials involving hydroxychloroquine have demonstrated the safety of targeting autophagy, but efficacy could be improved.Autophagy regulates tumor immunity.Novel autophagy inhibitors are entering clinical trials. Autophagy is a cellular homeostasis mechanism that fuels the proliferation and survival of advanced cancers by degrading and recycling organelles and proteins. Preclinical studies have identified that within an established tumor, tumor cell autophagy and host cell autophagy conspire to support tumor growth. A growing body of evidence suggests that autophagy inhibition can augment the efficacy of chemotherapy, targeted therapy, or immunotherapy to enhance tumor shrinkage. First-generation autophagy inhibition trials in cancer using the lysosomal inhibitor hydroxychloroquine (HCQ) have produced mixed results but have guided the way for the development of more potent and specific autophagy inhibitors in clinical trials. In this review, we will discuss the role of autophagy in cancer, newly discovered molecular mechanisms of the autophagy pathway, the effects of autophagy modulation in cancer and host cells, and novel autophagy inhibitors that are entering clinical trials.