DEVELOPMENT OF GLIEXP; A HIGH-THROUGHPUT EX VIVO DRUG SCREENING PLATFORM FOR GLIOBLASTOMA

Abstract AIMS With diminishing returns and common clinical failure rates from traditional preclinical animal-based drug discovery strategies, emphasis is being placed on alternative platforms, such as ex vivo approaches. Such approaches represent a departure both models more clinical-based strategies aim to address intra/inter-patient variability at an earlier stage of discovery. Additionally, they could also offer precise treatment stratification for patients within week surgery direct tailored course. One tumour group that significantly benefit are high-grade gliomas, which exhibit extensive heterogeneity, cellular plasticity therapy- resistant glioma stem cell (GSC) niches, where historic have failed generate new therapies leading 50-year stagnant dire survival around 15 months post-diagnosis. METHOD We developed optimized high-throughput screening platform; GliExP, maintains GSC populations using immediately dissociated fresh surgical tissue. RESULTS As proof-of-concept we standard-of-care chemoradiotherapy responses can correctly predict MGMT status based Temozolomide sensitivity. screened 30+ small molecule therapeutics compounds against 18 different patient’s tumours, including multi-region spatial het- erogeneity sampling several individual tumours. Drug further correlated transcriptomic genetic profiles. CONCLUSIONS Our data provides strong basis build upon GliExP incorporate combination-based oncology in tandem with important model triage experimental translation, delivering rapid identification effective gliomas.