Mechanisms of Resistance to Antibody-Drug Conjugates.

antibody-drug conjugate enfortumab vedotin linker monoclonal antibodies payload sacituzumab govitecan trastuzumab deruxtecan trastuzumab emtasine

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
02 Jun 2023
Historique:
received: 08 05 2023
revised: 29 05 2023
accepted: 30 05 2023
medline: 12 6 2023
pubmed: 10 6 2023
entrez: 10 6 2023
Statut: epublish

Résumé

The treatment of cancer patients has dramatically changed over the past decades with the advent of monoclonal antibodies, immune-checkpoint inhibitors, bispecific antibodies, and innovative T-cell therapy. Antibody-drug conjugates (ADCs) have also revolutionized the treatment of cancer. Several ADCs have already been approved in hematology and clinical oncology, such as trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), and sacituzumab govitecan (SG) for the treatment of metastatic breast cancer, and enfortumab vedotin (EV) for the treatment of urothelial carcinoma. The efficacy of ADCs is limited by the emergence of resistance due to different mechanisms, such as antigen-related resistance, failure of internalization, impaired lysosomal function, and other mechanisms. In this review, we summarize the clinical data that contributed to the approval of T-DM1, T-DXd, SG, and EV. We also discuss the different mechanisms of resistance to ADCs, as well as the ways to overcome this resistance, such as bispecific ADCs and the combination of ADCs with immune-checkpoint inhibitors or tyrosine-kinase inhibitors.

Identifiants

pubmed: 37298631
pii: ijms24119674
doi: 10.3390/ijms24119674
pmc: PMC10253543
pii:
doi:

Substances chimiques

Immune Checkpoint Inhibitors 0
Immunoconjugates 0
Ado-Trastuzumab Emtansine SE2KH7T06F

Types de publication

Journal Article Review

Langues

eng

Sous-ensembles de citation

IM

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Auteurs

Rita Khoury (R)

International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

Khalil Saleh (K)

International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

Nadine Khalife (N)

Department of Head and Neck Oncology, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

Mohamad Saleh (M)

Department of Hematology and Oncology, Lebanese American University Medical Center-Rizk Hopsital, Beirut 1100, Lebanon.

Claude Chahine (C)

International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

Rebecca Ibrahim (R)

International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

Axel Lecesne (A)

International Department, Gustave Roussy Cancer Campus, 94800 Villejuif, France.

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