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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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Autores principales: Mezni, Essia, Vicier, Cécile, Guerin, Mathilde, Sabatier, Renaud, Bertucci, François, Gonçalves, Anthony
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352740/
https://www.ncbi.nlm.nih.gov/pubmed/32545895
http://dx.doi.org/10.3390/cancers12061573
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author Mezni, Essia
Vicier, Cécile
Guerin, Mathilde
Sabatier, Renaud
Bertucci, François
Gonçalves, Anthony
author_facet Mezni, Essia
Vicier, Cécile
Guerin, Mathilde
Sabatier, Renaud
Bertucci, François
Gonçalves, Anthony
author_sort Mezni, Essia
collection PubMed
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.
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spelling pubmed-73527402020-07-15 New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices? Mezni, Essia Vicier, Cécile Guerin, Mathilde Sabatier, Renaud Bertucci, François Gonçalves, Anthony Cancers (Basel) Review 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. MDPI 2020-06-14 /pmc/articles/PMC7352740/ /pubmed/32545895 http://dx.doi.org/10.3390/cancers12061573 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Mezni, Essia
Vicier, Cécile
Guerin, Mathilde
Sabatier, Renaud
Bertucci, François
Gonçalves, Anthony
New Therapeutics in HER2-Positive Advanced Breast Cancer: Towards a Change in Clinical Practices?
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 Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352740/
https://www.ncbi.nlm.nih.gov/pubmed/32545895
http://dx.doi.org/10.3390/cancers12061573
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