Cargando…

Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer

The identification of the HER2 alteration as an actionable oncogenic driver in breast cancer has propelled the development of HER-targeting monoclonal antibodies (mAb) such as trastuzumab and pertuzumab, which led to dramatic improvements in survival outcomes. Lately, the great strides made toward d...

Descripción completa

Detalles Bibliográficos
Autores principales: Rassy, Elie, Rached, Layal, Pistilli, Barbara
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636477/
https://www.ncbi.nlm.nih.gov/pubmed/36334569
http://dx.doi.org/10.1016/j.breast.2022.10.016
_version_ 1784824952802770944
author Rassy, Elie
Rached, Layal
Pistilli, Barbara
author_facet Rassy, Elie
Rached, Layal
Pistilli, Barbara
author_sort Rassy, Elie
collection PubMed
description The identification of the HER2 alteration as an actionable oncogenic driver in breast cancer has propelled the development of HER-targeting monoclonal antibodies (mAb) such as trastuzumab and pertuzumab, which led to dramatic improvements in survival outcomes. Lately, the great strides made toward developing antibody-conjugation methods have led to the development of a new class of compelling compounds, the antibody-drug conjugates (ADCs) targeting HER2 which have profoundly transformed the treatment landscape of breast cancer. HER2-targeting ADCs, trastuzumab-emtansine and trastuzumab-deruxtecan, have improved the overall survival in the second and third-line settings with manageable adverse events. Other HER2-targeting ADCs using novel technological advances in the antibody, linker and/or payload conception have shown promising activity in preclinical and clinical studies and some of them are now being evaluated in larger clinical trials. Multiple challenges still impede the success of ADCs in breast cancer namely the lack of a comprehensive understanding of resistance mechanisms as well as the mechanisms of action of ADCs in special subgroups of patients such as those with low or ultra-low HER2 expression and patients with brain or leptomeningeal metastases (BM). In this framework, we review the approved indications and ongoing trials for HER2-targeting ADCs, across patient subgroups, including those with BM and discuss the associated potential mechanisms of action and resistance. Last, we provide an overview of the future perspectives involving HER2-targeting ADCs in breast cancer.
format Online
Article
Text
id pubmed-9636477
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-96364772022-11-06 Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer Rassy, Elie Rached, Layal Pistilli, Barbara Breast Article(s) from the Special Issue on: Antibody-drug Conjugates; Edited by Giuseppe Curigliano, Hope Rugo The identification of the HER2 alteration as an actionable oncogenic driver in breast cancer has propelled the development of HER-targeting monoclonal antibodies (mAb) such as trastuzumab and pertuzumab, which led to dramatic improvements in survival outcomes. Lately, the great strides made toward developing antibody-conjugation methods have led to the development of a new class of compelling compounds, the antibody-drug conjugates (ADCs) targeting HER2 which have profoundly transformed the treatment landscape of breast cancer. HER2-targeting ADCs, trastuzumab-emtansine and trastuzumab-deruxtecan, have improved the overall survival in the second and third-line settings with manageable adverse events. Other HER2-targeting ADCs using novel technological advances in the antibody, linker and/or payload conception have shown promising activity in preclinical and clinical studies and some of them are now being evaluated in larger clinical trials. Multiple challenges still impede the success of ADCs in breast cancer namely the lack of a comprehensive understanding of resistance mechanisms as well as the mechanisms of action of ADCs in special subgroups of patients such as those with low or ultra-low HER2 expression and patients with brain or leptomeningeal metastases (BM). In this framework, we review the approved indications and ongoing trials for HER2-targeting ADCs, across patient subgroups, including those with BM and discuss the associated potential mechanisms of action and resistance. Last, we provide an overview of the future perspectives involving HER2-targeting ADCs in breast cancer. Elsevier 2022-10-26 /pmc/articles/PMC9636477/ /pubmed/36334569 http://dx.doi.org/10.1016/j.breast.2022.10.016 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article(s) from the Special Issue on: Antibody-drug Conjugates; Edited by Giuseppe Curigliano, Hope Rugo
Rassy, Elie
Rached, Layal
Pistilli, Barbara
Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer
title Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer
title_full Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer
title_fullStr Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer
title_full_unstemmed Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer
title_short Antibody drug conjugates targeting HER2: Clinical development in metastatic breast cancer
title_sort antibody drug conjugates targeting her2: clinical development in metastatic breast cancer
topic Article(s) from the Special Issue on: Antibody-drug Conjugates; Edited by Giuseppe Curigliano, Hope Rugo
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9636477/
https://www.ncbi.nlm.nih.gov/pubmed/36334569
http://dx.doi.org/10.1016/j.breast.2022.10.016
work_keys_str_mv AT rassyelie antibodydrugconjugatestargetingher2clinicaldevelopmentinmetastaticbreastcancer
AT rachedlayal antibodydrugconjugatestargetingher2clinicaldevelopmentinmetastaticbreastcancer
AT pistillibarbara antibodydrugconjugatestargetingher2clinicaldevelopmentinmetastaticbreastcancer