CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives

Cancers

Armando Orlandi¹  Alessandra Cassano¹  Simone Scagnoli²  Giuseppe Tonini³  Francesco Pantano³  Luisa Carbognin⁴  Ida Paris⁴  Laura Pizzuti⁵  Eriseld Krasniqi⁵  Patrizia Vici⁵  Antonio Astone⁶  Andrea Botticelli⁷  Agnese Fabbri⁸  Ilaria Portarena⁹  Nello Salesi^1,10  Giuliana D’Auria^1,11  Teresa Gamucci^1,11  Michela Roberto^1,12  Paolo Marchetti^1,12  Alessandra Fabi^1,13  Paola Scavina^1,14  Mauro Minelli^1,14 

[1] Department of Medical Oncology, Catholic University of Sacred Heart, 00168 Rome, Italy;Department of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00185 Rome, Italy;Department of Oncology, University Campus Biomedico of Rome, 00155 Rome, Italy;Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, Italy;Division of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy;Division of Medical Oncology, Fatebenefratelli San Pietro Hospital, 00189 Rome, Italy;Medical Oncology Unit B, Policlinico Umberto I, 00161 Rome, Italy;Medical Oncology Unit, Belcolle Hospital, 01100 Viterbo, Italy;Medical Oncology Unit, Department of Systems Medicine, Tor Vergata Clinical Center University Hospital, 00133 Rome, Italy;Medical Oncology, S.M. Goretti Hospital, 04100 Latina, Italy;Medical Oncology, Sandro Pertini Hospital, 00157 Rome, Italy;Oncology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, Italy;Phase 1 Unit and Pre+cision Medicine, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy;San Giovanni Addolorata Hospital, 00184 Rome, Italy;

关键词: CDK4/6 inhibitors;    breast cancer;    endocrine therapy (ET);    advanced breast cancer (ABC);    endocrine resistance;   

DOI  :  10.3390/cancers13020332

来源: DOAJ

【 摘 要 】

Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer is the most common breast cancer subtype, and endocrine therapy (ET) remains its therapeutic backbone. Although anti-estrogen therapies are usually effective initially, approximately 50% of HR+ patients develop resistance to ET within their lifetime, ultimately leading to disease recurrence and limited clinical benefit. The recent addition of cyclin-dependent kinase 4 (CDK4) and CDK6 inhibitors (palbociclib, ribociclib, abemaciclib) to ET have remarkably improved the outcome of patients with HR+ advanced breast cancer (ABC) compared with anti-estrogens alone, by targeting the cell-cycle machinery and overcoming some aspects of endocrine resistance. However, which patients are the better candidates for these drugs, which are the main characteristics for a better selection of patients or if there are predictive biomarkers of response, is still unknown. In this review we reported the mechanism of action of CDK4/6 inhibitors as well as their potential mechanism of resistance, their implications in clinical practice and the forthcoming strategies to enhance their efficacy in improving survival and quality of life of patients affected with HR+, HER2−, ABC.

【 授权许可】

Unknown