Cyclin-dependent kinase 4/6 inhibitors in breast cancer therapy.

Abstract

To review the latest preclinical and clinical findings on the role of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors in breast cancer and update on the studies investigating the predictive biomarkers of response to CDK4/6 inhibitors. The retinoblastoma tumor suppressor (Rb) pathway is frequently deregulated in breast cancer and strategies to target this pathway have recently been proven to be effective in breast cancer patients. Preclinical and clinical data suggest that CDK4/6 inhibitors might be particularly useful in patients with hormone-receptor-positive or HER2-positive tumors, whereas the role of such inhibitors in triple-negative breast cancer is still controversial. Clinical trials are now investigating the safety and efficacy of different CDK4/6 inhibitors, mostly in breast cancer patients with hormone-receptor-positive tumors. Recent studies demonstrated that alterations in the cyclin D-CDK4-Rb pathway may have a role in primary resistance to CDK4/6 inhibitors. Target therapies have brought great improvements in the management of breast cancer patients. CDK4/6 inhibitors look promising in the treatment of patients with hormone-receptor-positive breast cancer, but it is of pivotal importance to identify which subgroup of patients would mostly benefit from CDK4/6 inhibition with biomarker-driven clinical trials.