CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives
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+ pat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/2/332 |
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| author | Michela Roberto Antonio Astone Andrea Botticelli Luisa Carbognin Alessandra Cassano Giuliana D’Auria Agnese Fabbri Alessandra Fabi Teresa Gamucci Eriseld Krasniqi Mauro Minelli Armando Orlandi Francesco Pantano Ida Paris Laura Pizzuti Ilaria Portarena Nello Salesi Simone Scagnoli Paola Scavina Giuseppe Tonini Patrizia Vici Paolo Marchetti |
| author_facet | Michela Roberto Antonio Astone Andrea Botticelli Luisa Carbognin Alessandra Cassano Giuliana D’Auria Agnese Fabbri Alessandra Fabi Teresa Gamucci Eriseld Krasniqi Mauro Minelli Armando Orlandi Francesco Pantano Ida Paris Laura Pizzuti Ilaria Portarena Nello Salesi Simone Scagnoli Paola Scavina Giuseppe Tonini Patrizia Vici Paolo Marchetti |
| author_sort | Michela Roberto |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T04:28:59Z |
| format | Article |
| id | doaj.art-aa4a3b0040174ba08f449d7cffd6e48d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T04:28:59Z |
| publishDate | 2021-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-aa4a3b0040174ba08f449d7cffd6e48d2023-12-03T13:37:38ZengMDPI AGCancers2072-66942021-01-0113233210.3390/cancers13020332CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future PerspectivesMichela Roberto0Antonio Astone1Andrea Botticelli2Luisa Carbognin3Alessandra Cassano4Giuliana D’Auria5Agnese Fabbri6Alessandra Fabi7Teresa Gamucci8Eriseld Krasniqi9Mauro Minelli10Armando Orlandi11Francesco Pantano12Ida Paris13Laura Pizzuti14Ilaria Portarena15Nello Salesi16Simone Scagnoli17Paola Scavina18Giuseppe Tonini19Patrizia Vici20Paolo Marchetti21Oncology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, ItalyDivision of Medical Oncology, Fatebenefratelli San Pietro Hospital, 00189 Rome, ItalyMedical Oncology Unit B, Policlinico Umberto I, 00161 Rome, ItalyDepartment of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, ItalyDepartment of Medical Oncology, Catholic University of Sacred Heart, 00168 Rome, ItalyMedical Oncology, Sandro Pertini Hospital, 00157 Rome, ItalyMedical Oncology Unit, Belcolle Hospital, 01100 Viterbo, ItalyPhase 1 Unit and Pre+cision Medicine, IRCCS Regina Elena National Cancer Institute, 00144 Rome, ItalyMedical Oncology, Sandro Pertini Hospital, 00157 Rome, ItalyDivision of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, ItalySan Giovanni Addolorata Hospital, 00184 Rome, ItalyDepartment of Medical Oncology, Catholic University of Sacred Heart, 00168 Rome, ItalyDepartment of Oncology, University Campus Biomedico of Rome, 00155 Rome, ItalyDepartment of Woman and Child Health and Public Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, 00168 Rome, ItalyDivision of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, ItalyMedical Oncology Unit, Department of Systems Medicine, Tor Vergata Clinical Center University Hospital, 00133 Rome, ItalyMedical Oncology, S.M. Goretti Hospital, 04100 Latina, ItalyDepartment of Medical and Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00185 Rome, ItalySan Giovanni Addolorata Hospital, 00184 Rome, ItalyDepartment of Oncology, University Campus Biomedico of Rome, 00155 Rome, ItalyDivision of Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, ItalyOncology Unit, Department of Clinical and Molecular Medicine, Sant’Andrea Hospital, Sapienza University of Rome, Via di Grottarossa 1035-1039, 00189 Rome, ItalyHormone 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.https://www.mdpi.com/2072-6694/13/2/332CDK4/6 inhibitorsbreast cancerendocrine therapy (ET)advanced breast cancer (ABC)endocrine resistance |
| spellingShingle | Michela Roberto Antonio Astone Andrea Botticelli Luisa Carbognin Alessandra Cassano Giuliana D’Auria Agnese Fabbri Alessandra Fabi Teresa Gamucci Eriseld Krasniqi Mauro Minelli Armando Orlandi Francesco Pantano Ida Paris Laura Pizzuti Ilaria Portarena Nello Salesi Simone Scagnoli Paola Scavina Giuseppe Tonini Patrizia Vici Paolo Marchetti CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives Cancers CDK4/6 inhibitors breast cancer endocrine therapy (ET) advanced breast cancer (ABC) endocrine resistance |
| title | CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives |
| title_full | CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives |
| title_fullStr | CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives |
| title_full_unstemmed | CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives |
| title_short | CDK4/6 Inhibitor Treatments in Patients with Hormone Receptor Positive, Her2 Negative Advanced Breast Cancer: Potential Molecular Mechanisms, Clinical Implications and Future Perspectives |
| title_sort | cdk4 6 inhibitor treatments in patients with hormone receptor positive her2 negative advanced breast cancer potential molecular mechanisms clinical implications and future perspectives |
| topic | CDK4/6 inhibitors breast cancer endocrine therapy (ET) advanced breast cancer (ABC) endocrine resistance |
| url | https://www.mdpi.com/2072-6694/13/2/332 |
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