Trastuzumab deruxtecan in breast cancer

[EN]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 DX...

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Detalles Bibliográficos
Autores: Martín, Miguel, Pandiella Alonso, Atanasio, Vargas-Castrillón, Emilio, Díaz Rodríguez, María Elena, Iglesias-Hernangómez, Teresa, Martínez Cano, Concha, Fernández-Cuesta, Inés, Winkow, Elena, Perelló, Maria Francesca
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Universidad de Salamanca (USAL)
Repositorio:GREDOS. Repositorio Institucional de la Universidad de Salamanca
OAI Identifier:oai:gredos.usal.es:10366/167788
Acceso en línea:http://hdl.handle.net/10366/167788
Access Level:acceso abierto
Palabra clave:Antibody-drug conjugate
HER2-low metastatic breast cancer
HER2-positive metastatic breast cancer
Trastuzumab deruxtecan
2302.06 Quimioterapia
Descripción
Sumario:[EN]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.