Targeting Cancer Stem Cells in Glioblastoma: A Systematic Review of Preclinical and Clinical Evidence

Abstract

Introduction: Glioblastoma (GBM) is a highly aggressive brain tumor with poor prognosis, attributed in part to a subpopulation of cancer stem cells (CSCs) that drive tumor recurrence and resistance. This review examines strategies targeting GBM CSCs. Methods: We reviewed preclinical and clinical studies targeting CSC-specific pathways (e.g., Notch, Wnt, Hedgehog), surface markers (e.g., CD133), or metabolic vulnerabilities. The search included PubMed and oncology-specific databases. Results: Numerous preclinical studies demonstrated that inhibiting CSC pathways could reduce tumor growth and sensitize GBM to radiation and chemotherapy. However, clinical translation has been challenging. Early-phase trials of CSC-targeting agents have shown limited monotherapy efficacy, often due to pathway redundancy and toxicity. Discussion: The concept of targeting CSCs in GBM is biologically sound but clinically difficult. A multi-pronged approach that targets both the bulk tumor and the CSC population simultaneously may be required for therapeutic success. Conclusion: While targeting cancer stem cells remains a highly promising strategy for glioblastoma, current approaches have yet to yield significant clinical benefit, highlighting the need for novel targets and combination therapies.