Frontiers in Cell and Developmental Biology (Mar 2023)

CDK4/6 inhibitor resistance in estrogen receptor positive breast cancer, a 2023 perspective

  • Fiona H. Zhou,
  • Fiona H. Zhou,
  • Teesha Downton,
  • Teesha Downton,
  • Allegra Freelander,
  • Allegra Freelander,
  • Joshua Hurwitz,
  • Joshua Hurwitz,
  • C. Elizabeth Caldon,
  • C. Elizabeth Caldon,
  • Elgene Lim,
  • Elgene Lim

DOI
https://doi.org/10.3389/fcell.2023.1148792
Journal volume & issue
Vol. 11

Abstract

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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.

Keywords