Mechanisms of sensitivity and resistance to CDK4/CDK6 inhibitors in hormone receptor-positive breast cancer treatment.

Autor: Glaviano A; Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo 90123, Italy., Wander SA; Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Baird RD; Cancer Research UK Cambridge Centre, Hills Road, Cambridge CB2 0QQ, UK., Yap KC; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore., Lam HY; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore., Toi M; School of Medicine, Kyoto University, Kyoto, Japan., Carbone D; Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo 90123, Italy., Geoerger B; Gustave Roussy Cancer Center, Department of Pediatric and Adolescent Oncology, Inserm U1015, Université Paris-Saclay, Villejuif, France., Serra V; Experimental Therapeutics Group, Vall d'Hebron Institute of Oncology, Barcelona, Spain., Jones RH; Cardiff University and Velindre Cancer Centre, Museum Avenue, Cardiff CF10 3AX, UK., Ngeow J; Lee Kong Chian School of Medicine (LKCMedicine), Nanyang Technological University, Experimental Medicine Building, 636921, Singapore; Cancer Genetics Service (CGS), National Cancer Centre Singapore, 168583, Singapore., Toska E; Department of Biochemistry and Molecular Biology, Johns Hopkins School of Public Health, Baltimore, MD, USA., Stebbing J; School of Life Sciences, Anglia Ruskin University, Cambridge, UK; Division of Cancer, Imperial College London, Hammersmith Campus, London, UK., Crasta K; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, 117593, Singapore; Healthy Longetivity Translational Program, Yong Loo Lin School of Medicine, National University of Singapore, 117456, Singapore., Finn RS; Department of Oncology, Geffen School of Medicine, University of California, Los Angeles, CA, USA., Diana P; Department of Biological, Chemical and Pharmaceutical Sciences and Technologies, University of Palermo, Palermo 90123, Italy., Vuina K; MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK., de Bruin RAM; MRC Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, UK., Surana U; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; SiNOPSEE Therapeutics Pte Ltd, A⁎STARTCentral, 139955, Singapore., Bardia A; Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA., Kumar AP; Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore. Electronic address: apkumar@nus.edu.sg.
Jazyk: angličtina
Zdroj: Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy [Drug Resist Updat] 2024 Sep; Vol. 76, pp. 101103. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1016/j.drup.2024.101103
Abstrakt: Cell cycle dysregulation is a hallmark of cancer that promotes eccessive cell division. Cyclin-dependent kinase 4 (CDK4) and cyclin-dependent kinase 6 (CDK6) are key molecules in the G1-to-S phase cell cycle transition and are crucial for the onset, survival, and progression of breast cancer (BC). Small-molecule CDK4/CDK6 inhibitors (CDK4/6i) block phosphorylation of tumor suppressor Rb and thus restrain susceptible BC cells in G1 phase. Three CDK4/6i are approved for the first-line treatment of patients with advanced/metastatic hormone receptor-positive (HR + )/human epidermal growth factor receptor 2-negative (HER2 - ) BC in combination with endocrine therapy (ET). Though this has improved the clinical outcomes for survival of BC patients, there is no established standard next-line treatment to tackle drug resistance. Recent studies suggest that CDK4/6i can modulate other distinct effects in both BC and breast stromal compartments, which may provide new insights into aspects of their clinical activity. This review describes the biochemistry of the CDK4/6-Rb-E2F pathway in HR + BC, then discusses how CDK4/6i can trigger other effects in BC/breast stromal compartments, and finally outlines the mechanisms of CDK4/6i resistance that have emerged in recent preclinical studies and clinical cohorts, emphasizing the impact of these findings on novel therapeutic opportunities in BC.
Competing Interests: Declaration of Competing Interest S.A.W.: Consulting/Advisory Board: Foundation Medicine, Eli Lilly, Novartis, Astrazeneca, Biovica, Hologic, Pfizer, Puma Biotechnology; Education/Speaking: Guardant Health, Eli Lilly, 2ndMD; Institutional Research Support: Genentech, Eli Lilly, Pfizer, Pfizer, Nuvation Bio, Regor Therapeutics. A.B.: Consultant/Advisory board of: Pfizer, Novartis, Genentech, Merck, Radius Health, Immunomedics/Gilead, Sanofi, Daiichi Pharma/Astra Zeneca, Phillips, Eli Lilly, Foundation Medicine. Contracted Research/Grant (to institution): Genentech, Novartis, Pfizer, Merck, Sanofi, Radius Health, Immunomedics/Gilead, Daiichi Pharma/Astra Zeneca, Eli Lilly. Other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Databáze: MEDLINE
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