Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review.

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Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review.

Int J Cancer. 2018 Nov 26;:

Authors: Pandey K, An HJ, Kim SK, Lee SA, Kim S, Lim SM, Kim GM, Sohn J, Moon YW

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. This article is protected by copyright. All rights reserved.

PMID: 30478914 [PubMed - as supplied by publisher]

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