Novel ADCs and Strategies to Overcome Resistance to Anti-HER2 ADCs

During recent years, a number of new compounds against HER2 have reached clinics, improving the prognosis and quality of life of HER2-positive breast cancer patients. Nonetheless, resistance to standard-of-care drugs has motivated the development of novel agents, such as new antibody-drug conjugates...

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Bibliographic Details
Published in:Cancers 2021-12, Vol.14 (1), p.154
Main Authors: Díaz-Rodríguez, Elena, Gandullo-Sánchez, Lucía, Ocaña, Alberto, Pandiella, Atanasio
Format: Article
Language:English
Subjects:
Antibodies
Antigens
Antitumor agents
Apoptosis
Breast cancer
Cell cycle
Clinical trials
Cytotoxic agents
Cytotoxicity
Drug development
Drug resistance
ErbB-2 protein
Kinases
Medical prognosis
Membrane proteins
Metastasis
Patients
Payloads
Permeability
Polymerization
Prognosis
Protein-tyrosine kinase
Quality of life
Review
Trastuzumab
Tumors
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Summary:During recent years, a number of new compounds against HER2 have reached clinics, improving the prognosis and quality of life of HER2-positive breast cancer patients. Nonetheless, resistance to standard-of-care drugs has motivated the development of novel agents, such as new antibody-drug conjugates (ADCs). The latter are a group of drugs that benefit from the potency of cytotoxic agents whose action is specifically guided to the tumor by the target-specific antibody. Two anti-HER2 ADCs have reached the clinic: trastuzumab-emtansine and, more recently, trastuzumab-deruxtecan. In addition, several other HER2-targeted ADCs are in preclinical or clinical development, some of them with promising signs of activity. In the present review, the structure, mechanism of action, and potential resistance to all these ADCs will be described. Specific attention will be given to discussing novel strategies to circumvent resistance to ADCs.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers14010154