New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?
Over the last few decades, improved knowledge of oncogenic activation mechanisms of HER2 protein has led to the development of HER2 targeted therapies that are currently commonly used in HER2-positive advanced breast cancer, such as trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine....
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/6/1573 |
| _version_ | 1797565348339253248 |
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| author | Essia Mezni Cécile Vicier Mathilde Guerin Renaud Sabatier François Bertucci Anthony Gonçalves |
| author_facet | Essia Mezni Cécile Vicier Mathilde Guerin Renaud Sabatier François Bertucci Anthony Gonçalves |
| author_sort | Essia Mezni |
| collection | DOAJ |
| description | Over the last few decades, improved knowledge of oncogenic activation mechanisms of HER2 protein has led to the development of HER2 targeted therapies that are currently commonly used in HER2-positive advanced breast cancer, such as trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine. The management of this breast cancer subgroup has thus been revolutionized and its prognosis has changed dramatically. Nevertheless, HER2-positive advanced breast cancer remains an incurable disease and resistance to conventional anti-HER2 drugs is almost unavoidable. Nowadays, biochemical and pharmaceutical advances are meeting the challenge of developing increasingly sophisticated therapies directed against HER2, including novel anti HER2 antibodies with increased affinity. New antibody-drug conjugates (ADC) with more advanced pharmacological properties, and dual targeting of epitopes via bispecific monoclonal antibodies are also emerging. In addition, more potent and more specific HER2 tyrosine kinase inhibitors have shown interesting outcomes and are under development. Finally, researchers’ interest in tumor microenvironment, particularly tumor-infiltrating lymphocytes, and the major role that signaling pathways, such as the PI3K/AKT/mTOR pathway, play in the development of resistance to anti-HER2 therapies have spurred the development of clinical trials evaluating innovative combinations of anti-HER2 with PD-1/PDL-1, CDK4/6 and PI3K inhibitors. However, several questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches. |
| first_indexed | 2024-03-10T19:10:53Z |
| format | Article |
| id | doaj.art-2965ef3c912a4241908e771c697e9ced |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T19:10:53Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2965ef3c912a4241908e771c697e9ced2023-11-20T03:46:49ZengMDPI AGCancers2072-66942020-06-01126157310.3390/cancers12061573New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?Essia Mezni0Cécile Vicier1Mathilde Guerin2Renaud Sabatier3François Bertucci4Anthony Gonçalves5Department of Medical Oncology, Inserm U1068, CNRS UMR7258, Institute Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, FranceDepartment of Medical Oncology, Inserm U1068, CNRS UMR7258, Institute Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, FranceDepartment of Medical Oncology, Inserm U1068, CNRS UMR7258, Institute Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, FranceDepartment of Medical Oncology, Inserm U1068, CNRS UMR7258, Institute Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, FranceDepartment of Medical Oncology, Inserm U1068, CNRS UMR7258, Institute Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, FranceDepartment of Medical Oncology, Inserm U1068, CNRS UMR7258, Institute Paoli-Calmettes, Aix-Marseille University, 13009 Marseille, FranceOver the last few decades, improved knowledge of oncogenic activation mechanisms of HER2 protein has led to the development of HER2 targeted therapies that are currently commonly used in HER2-positive advanced breast cancer, such as trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine. The management of this breast cancer subgroup has thus been revolutionized and its prognosis has changed dramatically. Nevertheless, HER2-positive advanced breast cancer remains an incurable disease and resistance to conventional anti-HER2 drugs is almost unavoidable. Nowadays, biochemical and pharmaceutical advances are meeting the challenge of developing increasingly sophisticated therapies directed against HER2, including novel anti HER2 antibodies with increased affinity. New antibody-drug conjugates (ADC) with more advanced pharmacological properties, and dual targeting of epitopes via bispecific monoclonal antibodies are also emerging. In addition, more potent and more specific HER2 tyrosine kinase inhibitors have shown interesting outcomes and are under development. Finally, researchers’ interest in tumor microenvironment, particularly tumor-infiltrating lymphocytes, and the major role that signaling pathways, such as the PI3K/AKT/mTOR pathway, play in the development of resistance to anti-HER2 therapies have spurred the development of clinical trials evaluating innovative combinations of anti-HER2 with PD-1/PDL-1, CDK4/6 and PI3K inhibitors. However, several questions remain unresolved, like the optimal management of HER2-positive/HR-positive advanced breast cancer and the identification of predictive biomarkers to better define populations that can benefit most from these new therapies and approaches.https://www.mdpi.com/2072-6694/12/6/1573advanced breast cancerHER2-positive diseaseanti-HER2 treatment |
| spellingShingle | Essia Mezni Cécile Vicier Mathilde Guerin Renaud Sabatier François Bertucci Anthony Gonçalves New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices? Cancers advanced breast cancer HER2-positive disease anti-HER2 treatment |
| title | New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices? |
| title_full | New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices? |
| title_fullStr | New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices? |
| title_full_unstemmed | New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices? |
| title_short | New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices? |
| title_sort | new therapeutics in her2 positive advanced breast cancer towards a change in clinical practices |
| topic | advanced breast cancer HER2-positive disease anti-HER2 treatment |
| url | https://www.mdpi.com/2072-6694/12/6/1573 |
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