Cracking the Genomic Code of CDK4/6 Inhibitor Resistance

Author:

Wander Seth A.1ORCID,Bardia Aditya2ORCID

Affiliation:

1. 1Massachusetts General Hospital Cancer Center, Boston, Massachusetts.

2. 2David Geffen School of Medicine at UCLA and UCLA Health Jonsson Comprehensive Cancer Center, Los Angeles, California.

Abstract

Summary The therapeutic approach to metastatic hormone receptor–positive, human epidermal growth factor-2–negative metastatic breast cancer (HR+/HER2− MBC) has evolved rapidly over recent years. The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have become first-line targeted agents of choice, in combination with an antiestrogen. Simultaneously, the clinical landscape of therapeutic options has been rapidly shifting, with novel antiestrogens, signal transduction inhibitors, and next-generation CDK inhibitors in various stages of development. Given these dynamic changes, understanding the genomic and molecular landscape of resistance to currently available antiestrogen therapy and CDK4/6 inhibitors represents a major focus of translational breast cancer research globally. See related article by Goetz et al., p. 2233

Publisher

American Association for Cancer Research (AACR)

Reference21 articles.

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4. ESR1 mutations-a mechanism for acquired endocrine resistance in breast cancer;Jeselsohn;Nat Rev Clin Oncol,2015

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