Georgetown Scientific Research Journal GSR Journal
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Research Articles

Vol. 1 No. 1 (2021): Georgetown Scientific Research Journal: Fall 2020 Issue

Evaluating the Efficacy of Targeted Inhibitor Therapeutics for Sonic Hedgehog Medulloblastoma: Significant Milestones and Current Limitations

December 16, 2020


Medulloblastoma (MB) is the most common pediatric brain tumor with the Sonic Hedgehog (SHH) subtype accounting for 30% of all diagnoses. The current standard treatment regimen includes high doses of toxic chemotherapy and radiation, as well as surgical resection, motivating the need for alternative therapies which do not generate deleterious effects on patients. The purpose of this literature review was to evaluate the most recent developments in the efficacy of targeted therapeutics in treatment of SHH MB, specifically focusing on small molecule inhibitors targeting the Sonic Hedgehog pathway. The sources analyzed in this review include case studies, preclinical and clinical studies, and other review papers that investigate the mechanism and value of five SHH inhibitors: vismodegib, sonidegib, glasdegib, temozolomide, and GANT-61. Novel discoveries have highlighted that inhibitor therapeutics effectively target aberrant activity of the SHH pathway at various stages, thereby diminishing tumor progression and metastasis. Through evaluation of the inhibitors, it was determined that they are promising targeted therapeutics for SHH MB, despite their limitations. These limitations include drug resistance, molecular heterogeneity of SHH-driven tumors, and poor drug properties. More research will be needed to overcome these obstacles for clinical use, but the investment is warranted given the promise of these inhibitors. Future research should seek to establish optimal dosage and timing of intervention, further delineate the genetic basis for SHH MB, and investigate potential combination therapies with SHH inhibitors.