Trastuzumab deruxtecan in breast cancer

Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) consisting of a humanised, anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody covalently linked to a topoisomerase I inhibitor cytotoxic payload (DXd). The high drug-to-antibody ratio (8:1) ensures a high DXd co...

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Detalhes bibliográficos
Autores: Martín, Miguel, Pandiella, Atanasio, Vargas-Castrillón, Emilio, Díaz-Rodríguez, Elena, Iglesias-Hernangómez, Teresa, Martínez Cano, Concha, Fernández-Cuesta, Inés, Winkow, Elena, Perelló, Maria Francesca
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Recursos:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/364977
Acesso em linha:http://hdl.handle.net/10261/364977
Access Level:acceso abierto
Palavra-chave:Antibody-drug conjugate
HER2-low metastatic breast cancer
HER2-positive metastatic breast cancer
Trastuzumab deruxtecan
Descrição
Resumo:Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate (ADC) consisting of a humanised, anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibody covalently linked to a topoisomerase I inhibitor cytotoxic payload (DXd). The high drug-to-antibody ratio (8:1) ensures a high DXd concentration is delivered to target tumour cells, following internalisation of T-DXd and subsequent cleavage of its tetrapeptide-based linker. DXd’s membrane-permeable nature enables it to cross cell membranes and potentially exert antitumour activity on surrounding tumour cells regardless of HER2 expression. T-DXd’s unique mechanism of action is reflected in its efficacy in clinical trials in patients with HER2-positive advanced breast cancer (in heavily pretreated populations and in those previously treated with a taxane and trastuzumab), as well as HER2-low metastatic breast cancer. Thus, ADCs such as T-DXd have the potential to change the treatment paradigm of targeting HER2 in metastatic breast cancer, including eventually within the adjuvant/neoadjuvant setting.