American Association for Cancer Research (AACR 2024) April 5-10, 2024 - part 3
BORTEM-17 interim analysis results and small molecule inhibitor targeting CSPG4/NG2 in glioblastoma at American Association for Cancer Research (AACR 2024) April 5-10, 2024
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PhD Student Lasse Neset
PhD Student Lasse Neset presented a poster titeld ‘Cryo-EM structure-based small molecule inhibitor drugs targeting CSPG4/NG2 in glioblastoma’.
The study investigates the therapeutic potential of targeting CSPG4, a putative biomarker for aggressive behaviour in glioblastoma. A 13 bp mutation was identified that reduced protein expression, cell growth in vitro and in vivo in mice. We hypothesize that a small-molecule inhibitor that binds to this region of CSPG4 proteoglycan may induce the same phenotype as the mutation. In silico analysis based on the Cryo-EM structure of domain 1 of CSPG4 identified 5-azacytidine and L-DOPA, drugs that bind the proteoglycan, reducing cell proliferation, clonogenecity and migration in vitro.
These findings suggest a potential to develop small-molecule inhibitors to disrupt CSPG4/NG2 function for GBM treatment. Cryo-EM-based structural and biochemical/physical analyses are ongoing to identify new target regions for drug development.
Abstract: https://aacrjournals.org/cancerres/article/84/6_Supplement/4494/738433
