Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Enhancing Anti-Cancer Therapy with Selective Autophagy Inhibitors by Targeting Protective Autophagy

  • Min Ju, Lee (Department of Medical Lifescience, College of Medicine, The Catholic University of Korea) ;
  • Jae-Sung, Park (Department of Neurosurgery, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea) ;
  • Seong Bin, Jo (Department of Medical Lifescience, College of Medicine, The Catholic University of Korea) ;
  • Young Ae, Joe (Department of Medical Lifescience, College of Medicine, The Catholic University of Korea)
  • Received : 2022.11.25
  • Accepted : 2022.12.06
  • Published : 2023.01.01
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Abstract

Autophagy is a process of eliminating damaged or unnecessary proteins and organelles, thereby maintaining intracellular homeostasis. Deregulation of autophagy is associated with several diseases including cancer. Contradictory dual roles of autophagy have been well established in cancer. Cytoprotective mechanism of autophagy has been extensively investigated for overcoming resistance to cancer therapies including radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Selective autophagy inhibitors that directly target autophagic process have been developed for cancer treatment. Efficacies of autophagy inhibitors have been tested in various pre-clinical cancer animal models. Combination therapies of autophagy inhibitors with chemotherapeutics are being evaluated in clinal trials. In this review, we will focus on genetical and pharmacological perturbations of autophagy-related proteins in different steps of autophagic process and their therapeutic benefits. We will also summarize combination therapies of autophagy inhibitors with chemotherapies and their outcomes in pre-clinical and clinical studies. Understanding of current knowledge of development, progress, and application of cytoprotective autophagy inhibitors in combination therapies will open new possibilities for overcoming drug resistance and improving clinical outcomes.

Keywords

Acknowledgement

This research was supported by a grant (NRF-2020R1A2C2006189) from the National Research Foundation of Korea grants funded by the Korean government.

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