Preclinical and clinical development of palbociclib and future perspectives
Cyclin-dependent kinases (CDKs) play a key role in cell cycle regulation, which makes them a clear therapeutic target to interfere with cell division and proliferation in cancer patients. Palbociclib, a specific inhibitor of CDK4/6 with outstanding clinical efficacy data and limited toxicity, has been recently approved for the treatment of hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative locally advanced or metastatic breast cancer, either in combination with an aromatase inhibitor or in combination with fulvestrant in women who have received prior endocrine therapy. This review describes the mechanism of action, preclinical experiences and clinical data of palbociclib, with a special focus on integrating this data with the positioning of palbociclib in the current clinical guidelines for advanced HR-positive/HER2-negative breast cancer. Aspects of the ongoing major studies are also presented, as well as future prospects in the development of palbociclib.
KeywordsCyclin Cell cycle Anti-tumor Breast cancer PI3K Palbociclib Cyclin-dependent kinases CDK4/6
The authors wish to thank Dr. Fernando Sánchez-Barbero from HealthCo S.L. (Madrid, Spain) for his help in the preparation of the manuscript. Pfizer provided comment on the first draft of this manuscript, but thereafter authors made all the decisions about its contents.
Compliance with ethical standards
Conflict of interest
The authors declare that they do not have any conflict of interest that may inappropriately influence this work.
The study has been performed in accordance with the ethical standards of the Declaration of Helsinki and its later amendments. This article does not contain any studies with human participants or animals performed by any of the authors.
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