{"doi":"10.1093/neuonc/noad205","title":"Systematic characterization of antibody–drug conjugate targets in central nervous system tumors","abstract":"BACKGROUND: Antibody-drug conjugates (ADCs) enhance the specificity of cytotoxic drugs by directing them to cells expressing target antigens. Multiple ADCs are FDA-approved for solid and hematologic malignancies, including those expressing HER2, TROP2, and NECTIN4. Recently, an ADC targeting HER2 (Trastuzumab-Deruxtecan) increased survival and reduced growth of brain metastases in treatment-refractory metastatic breast cancer, even in tumors with low HER2 expression. Thus, low-level expression of ADC targets may be sufficient for treatment responsiveness. However, ADC target expression is poorly characterized in many central nervous system (CNS) tumors. METHODS: We analyzed publicly available RNA-sequencing and proteomic data from the children's brain tumor network (N = 188 tumors) and gene-expression-omnibus RNA-expression datasets (N = 356) to evaluate expression of 14 potential ADC targets that are FDA-approved or under investigation in solid cancers. We also used immunohistochemistry to measure the levels of HER2, HER3, NECTIN4, TROP2, CLDN6, CLDN18.2, and CD276/B7-H3 protein in glioblastoma, oligodendroglioma, meningioma, ependymoma, pilocytic astrocytoma, medulloblastoma, atypical teratoid/rhabdoid tumor (AT/RT), adamantinomatous craniopharyngioma (ACP), papillary craniopharyngioma (PCP), and primary CNS lymphoma (N = 575). RESULTS: Pan-CNS analysis showed subtype-specific expression of ADC target proteins. Most tumors expressed HER3, B7-H3, and NECTIN4. Ependymomas strongly expressed HER2, while meningiomas showed weak-moderate HER2 expression. ACP and PCP strongly expressed B7-H3, with TROP2 expression in whorled ACP epithelium. AT/RT strongly expressed CLDN6. Glioblastoma showed little subtype-specific marker expression, suggesting a need for further target development. CONCLUSIONS: CNS tumors exhibit subtype-specific expression of ADC targets including several FDA-approved for other indications. Clinical trials of ADCs in CNS tumors may therefore be warranted.","journal":"Neuro-Oncology","year":2023,"id":321508,"datarank":0.5709993734655481,"base_score":3.8066624897703196,"endowment":3.8066624897703196,"self_citation_contribution":0.5709993734655481,"citation_network_contribution":0.0,"self_endowment_contribution":0.5709993734655481,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":44,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1033632,"name":"Jong Suk Lee","orcid":"0009-0008-4460-7118","position":1,"is_corresponding":false},{"id":1033633,"name":"Sabrina Chan","orcid":"0000-0002-4557-2972","position":2,"is_corresponding":false},{"id":548134,"name":"Terri Woo","orcid":null,"position":3,"is_corresponding":false},{"id":1034137,"name":"Jacquelyn Jones","orcid":null,"position":4,"is_corresponding":false},{"id":25330,"name":"Sanda Alexandrescu","orcid":"0000-0001-9246-4184","position":5,"is_corresponding":false},{"id":25299,"name":"Patrick Y. Wen","orcid":"0000-0002-0774-7700","position":6,"is_corresponding":false},{"id":24147,"name":"Peter K. Sorger","orcid":"0000-0002-3364-1838","position":7,"is_corresponding":false},{"id":1412,"name":"Keith L. Ligon","orcid":"0000-0002-7733-600X","position":8,"is_corresponding":false},{"id":70392,"name":"Sandro Santagata","orcid":"0000-0002-7528-9668","position":9,"is_corresponding":false},{"id":697031,"name":"Shannon Coy","orcid":"0000-0003-0033-9031","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:07:32.611759Z","pmid":"37870091","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}