학술논문
CDK4/6 inhibition in hormone receptor-positive/HER2-negative breast cancer: Biological and clinical aspects.
Document Type
Academic Journal
Author
Wekking D; Amsterdam UMC, Location Academic Medical Centre, University of Amsterdam, Amsterdam, the Netherlands. Electronic address: d.wekking@amsterdamumc.nl.; Leoni VP; Metabolomics Unit, Department of Biomedical Sciences, University of Cagliari, Italy.; Lambertini M; Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genova, Italy; Department of Medical Oncology, UOC Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy.; Dessì M; Medical Oncology AOU Cagliari Policlinico Duilio Casula, Monserrato, Cagliari, Italy.; Pretta A; Medical Oncology Unit, University Hospital and University of Cagliari, Italy.; Cadoni A; Medical Oncology Unit, University Hospital and University of Cagliari, Italy.; Atzori L; Metabolomics Unit, Department of Biomedical Sciences, University of Cagliari, Italy.; Scartozzi M; Medical Oncology AOU Cagliari Policlinico Duilio Casula, Monserrato, Cagliari, Italy; Medical Oncology Unit, University Hospital and University of Cagliari, Italy.; Solinas C; Medical Oncology AOU Cagliari Policlinico Duilio Casula, Monserrato, Cagliari, Italy.
Source
Publisher: Elsevier Science Country of Publication: England NLM ID: 9612306 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0305 (Electronic) Linking ISSN: 13596101 NLM ISO Abbreviation: Cytokine Growth Factor Rev Subsets: MEDLINE
Subject
Language
English
Abstract
A dysregulated cell division, one of the key hallmarks of cancer, results in uncontrolled cellular proliferation. This aberrant process, mediated by a dysregulated cell-cycle machinery and overactivation of cyclin-dependent kinase (CDK) 4 and 6, can potentially promote tumorigenesis. The clinical application of CDK 4/6 inhibitors, developed to inhibit cell-cycle progression, in the treatment regimens of breast cancer (BC) patients is expanding. Currently, three agents, ribociclib, palbociclib, and abemaciclib, are approved for treating patients with hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic BC. In addition, abemaciclib is FDA and EMA-approved for patients with hormone receptor-positive HER2-negative, node-positive, early BC at high risk of recurrence. Emerging data suggest potential anti-tumor effects beyond cell cycle arrest, providing novel insights into the agent's mechanisms of action. As a result, a broader application of the CDK4/6 inhibitors in patients with cancer is achieved, contributing to enhanced optimized treatment in the adjuvant and neoadjuvant settings. Herein, the immunomodulatory activities of CDK4/6 inhibitors, their impact on the cell's metabolic state, and the effect on the decision of the cell to undergo quiescence or senescence are discussed. Moreover, this review provides an update on clinical trial outcomes and the differences in the underlying mechanisms between the distinct CDK4/6 inhibitors.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. Cinzia Solinas reports travel grants from Ipsen and Eli Lilly. All other authors have no conflict of interest to declare related to the present topic.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Matteo Lambertini reports advisory role for Roche, Lilly, Novartis, Astrazeneca, Pfizer, Seagen, Gilead, MSD and Exact Sciences and speaker honoraria from Roche, Lilly, Novartis, Pfizer, Sandoz, Libbs, Daiichi Sankyo, Knight and Takeda, Travel Grants from Gilead and Daiichi Sankyo, and research support (to the Institution) from Gilead outside the submitted work. Cinzia Solinas reports travel grants from Ipsen and Eli Lilly. All other authors have no conflict of interest to declare related to the present topic.
(Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)