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Palbociclib: an evidence-based review of its potential in the treatment of breast cancer

Authors Cadoo K, Gucalp A, Traina T

Received 5 March 2014

Accepted for publication 17 April 2014

Published 4 August 2014 Volume 2014:6 Pages 123—133


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 5

Video abstract presented by Karen A Cadoo.

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Karen A Cadoo, Ayca Gucalp, Tiffany A Traina

Breast Cancer Medicine Service, Memorial Sloan Kettering Cancer Center and Weill Medical College of Cornell University, New York, NY, USA

Abstract: Cellular proliferation, growth, and division following DNA (deoxyribonucleic acid) damage are tightly controlled by the cell-cycle regulatory machinery. This machinery includes cyclin-dependent kinases (CDKs) which complex with their cyclin partners, allowing the cell cycle to progress. The cell-cycle regulatory process plays a critical role in oncogenesis and in the development of therapeutic resistance; it is frequently disrupted in breast cancer, providing a rational target for therapeutic development. Palbociclib is a potent and selective inhibitor of CDK4 and -6 with significant activity in breast cancer models. Furthermore, it has been shown to significantly prolong progression-free survival when combined with letrozole in the management of estrogen receptor-positive metastatic breast cancer. In this article we review the cell cycle and its regulatory processes, their role in breast cancer, and the rationale for CDK inhibition in this disease. We describe the preclinical and clinical data relating to the activity of palbociclib in breast cancer and the plans for the future development of this agent.

Keywords: cell-cycle regulation, cyclin-dependent kinases, CDK4/6 inhibition

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