Sequencing Endocrine Therapy for Metastatic Breast Cancer: What Do We Do After Disease Progression on a CDK4/6 Inhibitor?

AbstractPurpose of ReviewCyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment landscape for patients with hormone receptor-positive (HR+) and HER2-negative (HER2 −) metastatic breast cancer (MBC). However, optimal therapy after CDK4/6 inhibitors is unknown. This review provides an update on recent understanding of potential resistance mechanisms to CDK4/6 inhibitors and therapeutic strategies.Recent FindingsCDK4/6 inhibitors are broadly effective for HR+/HER2 − MBC. However, intrinsic and acquired resistance is inevitable. Although there are no established clinical predictors of response aside from ER positivity, several cell cycle-specific and non-specific mechanisms have emerged as potential resistance biomarkers and therapeutic targets in recent stu dies. Examples include loss of function mutations inRB1 orFAT1, overexpression or amplification ofCDK6 and CCNE1, alterations ofFGFR, and PI3K/mTOR-mediated CDK2 activation.SummaryBiomarker studies and clinical trials targeting CDK4/6 inhibitor resistance are critical to improve treatments for HR+/HER2 − MBC.
Source: Current Oncology Reports - Category: Cancer & Oncology Source Type: research