CDK4/6 inhibitors: mechanisms of resistance and potential biomarkers of responsiveness in breast cancer

ÇETİN B. , Wabl C. A. , Gumusay O.

FUTURE ONCOLOGY, 2022 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Review
  • Publication Date: 2022
  • Doi Number: 10.2217/fon-2021-0842
  • Title of Journal : FUTURE ONCOLOGY
  • Keywords: biomarkers, CDK 4, 6 inhibitors, endocrine resistance, endocrine therapy, HER2-negative breast cancer, hormone receptor (HR) positive, resistance mechanisms, CYTOPLASMIC CYCLIN-E, PALBOCICLIB, THERAPY, ABEMACICLIB, PROGRESSION, FULVESTRANT, EXPRESSION, PATHWAY, COMBINATION, MULTICENTER


Hormone receptor (HR)-positive, HER2-negative tumors represent the most common form of metastatic breast cancer (MBC), and endocrine therapy has been the mainstay treatment for several decades. Recently, a novel drug class called CDK4/6 inhibitors in combination with endocrine therapy have remarkably improved the outcome of patients with HR-positive, HER2-negative MBC by targeting the cell cycle machinery and overcoming aspects of endocrine resistance. Several potential cell-cycle-specific and nonspecific mechanisms of resistance to CDK4/6 inhibitors have been reported in recent studies. This review discusses potential resistance mechanisms to CDK4/6 inhibitors, the use of biomarkers to guide treatment for HR-positive, HER2-negative MBC and possible approaches to overcome resistance to CDK4/6 inhibitors.