Molecular mechanisms of resistance to CDK4/6 inhibitors in breast cancer: A review. Issue 5 (7th January 2019)

• Record Type: Journal Article
• Authors: Pandey, Kamal; An, Hee‐Jung; Kim, Seung Ki; Lee, Seung Ah; Kim, Sewha; Lim, Sun Min; Kim, Gun Min; Sohn, Joohyuk; Moon, Yong Wha
• Is Part Of: International journal of cancer. Volume 145:Issue 5(2019)
• Page Start: 1179
• Page End: 1188
• Publication Date: 2019-01-07
• Subjects: CDK4/6 -- estrogen receptor‐positive breast cancer -- drug resistance; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32020
• Languages: English
• ISSNs: 0020-7136

Abstract

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.