Cyclin-Dependent Kinase 4/6 Inhibitors Against Breast Cancer

Mohammed   Al-Kassim   Hassan; Zeynep      Ates-Alagoz
Abstract

Breast cancer is the most frequently diagnosed and leading cause of cancer-related deaths in women worldwide. Based on global cancer (GLOBOCAN) 2020 statistics, 1 in 4 cancer cases and 1 in 6 cancer deaths are attributable to breast cancer, leading both in incidence and mortality. To address the increasing burden of cancer, novel therapeutic approaches that target key hallmarks of cancer are explored in cancer drug discovery. Cyclin-dependent kinase (CDK) inhibitors are generally purine and pyrimidine analogues validated for the treatment of cancer due to their unique roles in cancer deregulation and novel therapeutic potentials. So far, three orally administered, potent and highly selective CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) have been approved by the FDA for the targeted treatment of advanced or metastatic breast cancer in combination with endocrine therapy. Furthermore, several compounds derived from various synthetic scaffolds are being explored with promising results and positive outcomes in various stages of clinical trials. In this review, we highlight these CDK4/6 inhibitor compounds with potent anti-CDK4/6, in vitro and in vivo activities on breast cancer cells. With the remarkable prospects of these compounds, there is great optimism further novel CDK inhibitor compounds will be discovered in the future that could boost therapeutic options for cancer treatment.
Keywords: Cyclin-dependent kinase inhibitors, CDK4/6, cell cycle, cyclin-D, synthetic scaffolds, breast cancer.
Graphical Abstract

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Cite As
Mini-Reviews in Medicinal Chemistry

Cyclin-Dependent Kinase 4/6 Inhibitors Against Breast Cancer

Abstract

Graphical Abstract
