Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review |
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| Authors: | Kamal Pandey Hee-Jung An Seung Ki Kim Seung Ah Lee Sewha Kim Sun Min Lim Gun Min Kim Joohyuk Sohn Yong Wha Moon |
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| Institution: | 1. Medical Oncology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea;2. Department of Pathology, CHA Bundang Medical Center, CHA University, Seongnam, South Korea;3. Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, South Korea;4. Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea |
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| Abstract: | Deregulation of the cyclin D-CDK4/6-INK4-RB pathway leading to uncontrolled cell proliferation, is frequently observed in breast cancer. Currently, three selective CDK4/6 inhibitors have been FDA approved: palbociclib, ribociclib and abemaciclib. Despite promising clinical outcomes, intrinsic or acquired resistance to CDK4/6 inhibitors has limited the success of these treatments; therefore, the development of various strategies to overcome this resistance is of great importance. We highlight the various mechanisms that are directly or indirectly responsible for resistance to CDK4/6 inhibitors, categorizing them into two broad groups; cell cycle-specific mechanisms and cell cycle-nonspecific mechanisms. Elucidation of the diverse mechanisms through which resistance to CDK4/6 inhibitors occurs, may aid in the design of novel therapeutic strategies to improve patient outcomes. This review summarizes the currently available knowledge regarding mechanisms of resistance to CDK4/6 inhibitors, and possible therapeutic strategies that may overcome this resistance as well. |
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| Keywords: | CDK4/6 estrogen receptor-positive breast cancer drug resistance |
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