Cracking the Genomic Code of CDK4/6 Inhibitor Resistance.

The therapeutic approach to metastatic hormone-receptor positive, human epidermal growth factor-2 negative metastatic breast cancer (HR+/HER2- MBC) has evolved rapidly over recent years. The cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have become first-line targeted agents of choice, in combination with an anti-estrogen. Simultaneously, the clinical landscape of therapeutic options has been rapidly shifting, with novel anti-estrogens, signal transduction inhibitors, and next-generation CDK inhibitors in various staging of development. Given these dynamic changes, understanding the genomic and molecular landscape of resistance to currently available anti-estrogen therapy and CDK4/6 inhibitors represents a major focus of translational breast cancer research globally.