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


Cetin B., Wabl C. A., Gumusay Ö.

FUTURE ONCOLOGY, cilt.18, sa.9, ss.1143-1157, 2022 (SCI-Expanded) identifier identifier identifier identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 18 Sayı: 9
  • Basım Tarihi: 2022
  • Doi Numarası: 10.2217/fon-2021-0842
  • Dergi Adı: FUTURE ONCOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, CINAHL, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.1143-1157
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

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. Plain language summary Approximately 70% of breast cancers are hormone receptor (HR)-positive. A CDK4/6 inhibitor combined with endocrine therapy is the first-line standard of care for patients with HR-positive, HER-2 negative advanced breast cancer. Markers to predict the efficacy of CDK4/6 inhibitors in HR-positive, HER2-negative advanced breast cancer are limited. In this review, we summarize the use of CDK4/6 inhibitors in breast cancer, as well as possible approaches to overcome resistance to CDK4/6 inhibitors.