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Anti-cancer therapy with cyclin-dependent kinase inhibitors: impact and challenges

Published online by Cambridge University Press:  09 June 2021

Marika A. V. Reinius  and
Elizabeth Smyth Open the ORCID record for Elizabeth Smyth [Opens in a new window]
Marika A. V. Reinius
Affiliation:
Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, CambridgeCB2 0QQ, UK
Elizabeth Smyth*
Affiliation:
Department of Oncology, Cambridge University Hospitals NHS Foundation Trust, Hills Road, CambridgeCB2 0QQ, UK
*
Author for correspondence: Elizabeth Smyth, E-mail: [email protected]
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Abstract

The introduction of cyclin-dependent kinase 4/6 inhibitors (CKIs) has marked a major development in the standard treatment of advanced breast cancer. Extensive preclinical, translational and clinical research efforts into CKI agents are ongoing, and clinical application of this class of systemic anti-cancer therapy is anticipated to expand beyond metastatic breast cancer treatment. Emerging evidence indicates that mechanisms by which CKI agents exert their therapeutic effect transcend their initially expected impacts on cell cycle control into the realms of cancer immunology and metabolism. The recent expansion in our understanding of the multifaceted impact of CKIs on tumour biology has the potential to improve clinical study design, therapeutic strategies and ultimately patient outcomes. This review contextualises the current status of CKI therapy by providing an overview of the original and emerging insights into mechanisms of action and the evidence behind their current routine use in breast cancer management. Recent preclinical and clinical studies into CKIs across tumour types are discussed, including a synthesis of the more than 300 clinical trials of CKI-combination treatments registered as of November 2020. Key challenges and opportunities anticipated in the 2020s are explored, including treatment resistance, combination therapy strategies and potential biomarker development.

Keywords

Cancercell cyclecombination therapycyclin-dependent kinase inhibitorcyclin-dependent kinaseoncologytreatment resistance
Type
Review
Information
Expert Reviews in Molecular Medicine , Volume 23 , 2021 , e6
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press

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