Apoptosis Deregulation and the Development of Cancer Multi-Drug Resistance
European University Research Center, Nicosia 2404, Cyprus
Tumor Microenvironment, Metastasis and Experimental Therapeutics Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus
Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus
Department of Cell Biology and Biophysics, Faculty of Biology, National and Kapodistrian University of Athens, 15784 Athens, Greece
Department of Medical Pharmacology, Cancer immunology and Immunotherapy Unit, Medical School, Akdeniz University, Antalya 07058, Turkey
Author to whom correspondence should be addressed.
Academic Editor: Claudia M. Kowolik
Received: 29 July 2021
Revised: 21 August 2021
Accepted: 26 August 2021
Published: 28 August 2021
Despite recent therapeutic advances against cancer, many patients do not respond well or respond poorly, to treatment and develop resistance to more than one anti-cancer drug, a term called multi-drug resistance (MDR). One of the main factors that contribute to MDR is the deregulation of apoptosis or programmed cell death. Herein, we describe the major apoptotic pathways and discuss how pro-apoptotic and anti-apoptotic proteins are modified in cancer cells to convey drug resistance. We also focus on our current understanding related to the interactions between survival and cell death pathways, as well as on mechanisms underlying the balance shift towards cancer cell growth and drug resistance. Moreover, we highlight the role of the tumor microenvironment components in blocking apoptosis in MDR tumors, and we discuss the significance and potential exploitation of epigenetic modifications for cancer treatment. Finally, we summarize the current and future therapeutic approaches for overcoming MDR.