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Many CNS tumors may be vulnerable to existing antibody-drug conjugates

Sandro Santagata, Ludwig Cancer Research Harvard
Sandro Santagata
Shannon Coy, Ludwig Cancer Research Harvard
Shannon Coy

Antibody-drug conjugates (ADCs) enhance the specificity of cytotoxic drugs used for cancer treatment by directing them to cells expressing target antigens, potentially improving their efficacy and reducing their side effects. Many such drugs have in recent years been approved as cancer therapies and, as suggested by a recent study of patients with brain metastases of breast cancer, seem to work even when the targeted antigen is expressed at low levels. Still, the expression of ADC targets is poorly characterized in many central nervous system (CNS) tumors. Researchers led by Ludwig Harvard’s Sandro Santagata and Shannon Coy analyzed publicly available RNA-sequencing and proteomic data to evaluate the expression of 14 potential ADC targets that are FDA-approved or under investigation in solid cancers, examining ten different types of CNS tumors. Sandro, Shannon and their colleagues reported in Neuro-Oncology in October that most CNS tumors exhibit subtype-specific expression of ADC targets, including several that have been approved by the FDA for other indications. This opens the possibility of personalizing therapy for brain tumors, including rare ones, based on ADC target expression. Of high interest is glioblastoma, which expresses several potential ADC targets, although more work will be needed to find optimal targets for this highly aggressive malignancy. The researchers suggest that their findings support the clinical evaluation of ADCs for the treatment of many CNS tumors.

Systematic characterization of antibody-drug conjugate targets in central nervous system tumors
Neuro-Oncology, 2023 October 23

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