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Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer

Asghar, US; Kanani, R; Roylance, R; Mittnacht, S; (2022) Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer. JCO Precision Oncology , 6 pp. 1-13. 10.1200/po.21.00002. Green open access

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Abstract

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors have revolutionized the treatment of hormone-positive metastatic breast cancers (mBCs). They are currently established as standard therapies in combination with endocrine therapy as first- and second-line systemic treatment options for both endocrine-sensitive and endocrine-resistant mBC populations. In the first-line metastatic setting, the median progression-free survival for the three currently approved CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, with aromatase inhibitors is greater than 2 years (palbociclib 27.6 months; ribociclib 25.3 months; and abemaciclib 28.18 months). Although CDK4/6 inhibitors have significant clinical benefits and enable physicians to delay starting chemotherapy, they are expensive and can be associated with drug toxicities. Here, we have performed a systemic review of the reported molecular markers predictive of drug response including intrinsic and acquired resistance for CDK4/6 inhibition in mBC. The rapidly emerging molecular landscape is captured through next-generation sequencing of breast cancers (DNA with or without RNA), liquid biopsies (circulating tumor DNA), and protein analyses. Individual molecular candidates with robust and reliable evidence are discussed in more depth.

Type: Article
Title: Systematic Review of Molecular Biomarkers Predictive of Resistance to CDK4/6 Inhibition in Metastatic Breast Cancer
Open access status: An open access version is available from UCL Discovery
DOI: 10.1200/po.21.00002
Publisher version: http://doi.org/10.1200/po.21.00002
Language: English
Additional information: © 2022 by American Society of Clinical Oncology: Creative Commons Attribution Non-Commercial No Derivatives 4.0 License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: https://discovery.ucl.ac.uk/id/eprint/10141698
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