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Antibody–drug conjugates (ADCs), are a type of cancer treatment that combines monoclonal antibodies with a cytotoxic substance through a chemical linker, have already been approved for various cancer types. However, brain tumors can be difficult to treat due to the blood-brain barrier limiting drug delivery. Trastuzumab deruxtecan, an ADC targeting HER2, has shown promising results in treating brain metastases from HER2+ breast cancer, but depatuxizumab mafodotin, an ADC targeting EGFR, did not improve overall survival in patients with EGFR-amplified glioblastoma despite some patients showing positive radiological responses. This article summarizes the available data on ADCs for treating brain tumors, discusses their clinical implications, explores factors affecting their effectiveness in the brain, and proposes optimal trial designs to develop ADCs for glioma and brain metastasis treatment.
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