The role of CDK inhibitors in breast cancer therapy

Abstract

Cyclin D1 and cyclin-dependent protein kinases CDK4/6 are part of RB-pathway which plays a very important role in the regulation of cell cycle progression and cell death. d-type cyclins associate with cdk4 and 6 to phosphorylate the Rb protein. Hyperphosphorylation of Rb promotes the release of the E2F family of transcription factors that then promotes entry into S phase through activation of key target genes. CDK inhibitors are proteins that suppress CDK-cyclin protein kinase activity in the G1 phase of the cell cycle and promote G1 arrest in response to environmental or intracellular signals. A literature search of these topics was performed through PubMed. Results from preclinical and early-stage clinical trials support the efficiency of CDK inhibitors such palbociclib, abemaciclib and ribociclib for the treatment of human cancers - including breast cancer. The first-in-class CDK4/6 inhibitor, which significantly extended PFS in combination with endocrine therapy in the first and subsequent lines of treatment for steroid receptor -positive, HER2-negative advanced breast cancer is Palbociclib. Other inhibitors (abemaciclib, ribociclib) are still in clinical trials and are a very promising group of drugs.