Antibody-drug conjugates in breast cancer: overcoming resistance and boosting immune response

Antibody-drug conjugates (ADCs) have emerged as a revolutionary therapeutic class, combining the precise targeting ability of monoclonal antibodies with the potent cytotoxic effects of chemotherapeutics. Notably, ADCs have rapidly advanced in the field of breast cancer treatment. This innovative app...

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Bibliographic Details
Published in:The Journal of clinical investigation 2023-09, Vol.133 (18), p.1-10
Main Authors: Chang, Hannah L, Schwettmann, Blake, McArthur, Heather L, Chan, Isaac S
Format: Article
Language:English
Subjects:
Antibodies
Antibodies, Monoclonal
Antibody-drug conjugates
Antigens
Biomedical research
Brain cancer
Breast cancer
Breast Neoplasms - drug therapy
Cancer therapies
Cytotoxicity
Drug dosages
Drug resistance
Drug therapy
FDA approval
Female
Health aspects
Humans
Immune clearance
Immune response
Immunity
Immunoconjugates - pharmacology
Immunoconjugates - therapeutic use
Internalization
Metastasis
Monoclonal antibodies
Payloads
Physiological aspects
Prevention
Protein turnover
Proteins
Review
Toxicity
Tumor Microenvironment
Tumors
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Summary:Antibody-drug conjugates (ADCs) have emerged as a revolutionary therapeutic class, combining the precise targeting ability of monoclonal antibodies with the potent cytotoxic effects of chemotherapeutics. Notably, ADCs have rapidly advanced in the field of breast cancer treatment. This innovative approach holds promise for strengthening the immune system through antibody-mediated cellular toxicity, tumor-specific immunity, and adaptive immune responses. However, the development of upfront and acquired resistance poses substantial challenges in maximizing the effectiveness of these therapeutics, necessitating a deeper understanding of the underlying mechanisms. These mechanisms of resistance include antigen loss, derangements in ADC internalization and recycling, drug clearance, and alterations in signaling pathways and the payload target. To overcome resistance, ongoing research and development efforts are focused on urgently identifying biomarkers, integrating immune therapy approaches, and designing novel cytotoxic payloads. This Review provides an overview of the mechanisms and clinical effectiveness of ADCs, and explores their unique immune-boosting function, while also highlighting the complex resistance mechanisms and safety challenges that must be addressed. A continued focus on how ADCs impact the tumor microenvironment will help to identify new payloads that can improve patient outcomes.
ISSN:1558-8238
0021-9738
1558-8238
DOI:10.1172/JCI172156