Journal
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2023.1148792
Keywords
estrogen receptor; breast cancer; CDK4/6 inhibitor; endocrine therapy; resistance
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CDK4/6 inhibitors have revolutionized the treatment of ER+ breast cancer and are the standard first-line therapy. However, resistance to these inhibitors is a challenge and there is a need to understand the mechanisms of resistance to guide subsequent treatment decisions.
CDK4/6 inhibitors have become game-changers in the treatment of estrogen receptor-positive (ER+) breast cancer, and in combination with endocrine therapy are the standard of care first-line treatment for ER+/HER2-negative advanced breast cancer. Although CDK4/6 inhibitors prolong survival for these patients, resistance is inevitable and there is currently no clear standard next-line treatment. There is an urgent unmet need to dissect the mechanisms which drive intrinsic and acquired resistance to CDK4/6 inhibitors and endocrine therapy to guide the subsequent therapeutic decisions. We will review the insights gained from preclinical studies and clinical cohorts into the diverse mechanisms of CDK4/6 inhibitor action and resistance, and highlight potential therapeutic strategies in the context of CDK4/6 inhibitor resistance.
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