Clinical and Therapeutic Relevance of B7-H3 in Sarcomas: Molecular Insights from a Systematic Review.

Authors

Nouran Alwisi, Mohammad Abdel Hamid, Dahab Ghith, Salam Alshare, Lujain Adham, Samiha Sami, Giridhara Rathnaiah Babu, Semir Vranić

Published in

Journal of drug targeting. Pages 1-25. Sep 27, 2026. Epub Sep 27, 2026.

Abstract

Sarcomas are a heterogeneous group of mesenchymal malignancies characterized by substantial morphological and molecular diversity. Despite advances in surgery and systemic therapies, outcomes remain poor, underscoring the need for novel biomarkers and targeted therapies. We systematically assessed B7-H3 status in sarcomas. Forty-six studies were included (25 preclinical, 13 clinical, and eight mixed studies), most of which focused on osteosarcoma, rhabdomyosarcoma, and Ewing sarcoma. B7-H3 expression varied considerably across sarcoma subtypes and according to detection and scoring methods. The available evidence implicated B7-H3 in oncogenic transcriptional programs, miR-124 downregulation, matrix metalloproteinase-mediated shedding, and signaling pathways including PI3K-AKT-mTOR, MAPK, Wnt/β-catenin, and epithelial-mesenchymal transition. Emerging therapeutic strategies targeting B7-H3 included CAR T-cell therapies, antibody-drug conjugates, Fc-optimized antibodies, radiolabeled antibodies, and fluorescence-guided surgery. In clinical evidence, B7-H3 expression showed potential associations with disease progression and selected survival outcomes; however, findings were limited by heterogeneous methodologies and relatively sparse clinical data. B7-H3 represents a promising biomarker and therapeutic target in sarcomas, with substantial preclinical evidence supporting its biological and therapeutic relevance. However, standardized approaches to B7-H3 detection and scoring, together with well-designed prospective clinical studies, are needed to establish its prognostic and predictive value and determine the clinical efficacy of B7-H3-directed therapies.

PMID:
42801277
Bibliographic data and abstract were imported from PubMed on 27 Sep 2026.

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