Repurposing FDA-Approved Drugs for Temozolomide-Resistant IDH1 Mutant Glioma Using High-Throughput Miniaturized Screening on Droplet Microarray Chip.

ABSTRACT: To address the challenge of drug resistance and limited treatment options for recurrent gliomas with IDH1 mutations, a highly miniaturized screening of 2208 FDA-approved drugs is conducted using a high-throughput droplet microarray (DMA) platform. Two patient-derived temozolomide-resistant tumorspheres harboring endogenous IDH1 mutations (IDH1^mut ) are utilized. Screening identifies over 20 drugs, including verteporfin (VP), that significantly affected tumorsphere formation and viability. Proteomics analysis reveals that nuclear pore complex may be a potential VP target, suggesting a new mechanism of action independent of its known effects on YAP1. Knockdown experiments exclude YAP1 as a drug target in tumorspheres. Pathway analysis shows that NUP107 is a potential upstream regu

SUBMITTER: Cui H 

PROVIDER: S-EPMC11469062 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature