Ex-vivo drug screening of surgically resected glioma stem cells to replace murine avatars and provide personalise cancer therapy for glioblastoma patients

• DOI: 10.12688/f1000research.135809.2
• Publication Date: 2024-03-11T12:25:06Z
• Authors: Hannah Gagg; Sophie T. Williams; Samantha Conroy; Katie N. Myers; Connor McGarrity-...; Callum Jones; Thomas Helleday; Juha Rantala; Ola Rominiyi; Sarah J. Danson; Spencer J. Collis; Greg Wells
• Keywords: Ex vivo

<ns3:p>With diminishing returns and high clinical failure rates from traditional preclinical animal-based drug discovery strategies, more emphasis is being placed on alternative platforms. <ns3:italic>Ex vivo</ns3:italic> approaches represent a departure both models clinical-based strategies aim to address intra-tumoural inter-patient variability at an earlier stage of discovery. Additionally, these could also offer precise treatment stratification for patients within week tumour resection in order direct tailored therapy. One group that significantly benefit such <ns3:italic>ex are high-grade gliomas, which exhibit extensive heterogeneity, cellular plasticity therapy-resistant glioma stem cell (GSC) niches. Historic use murine-based tumours has largely failed generate new therapies, resulting relatively stagnant unacceptable survival around 12-15 months post-diagnosis over the last 50 years. The near universal DNA damaging chemoradiotherapy after surgical standard-of-care (SoC) therapy regimens provides opportunity improve current treatments if we can identify efficient combinations better reflect complex inter-/intra-tumour GSC inherent damage resistance mechanisms. We have therefore developed optimised high-throughput screening platform; GliExP, maintains populations using immediately dissociated fresh tissue. As proof-of-concept SoC responses screened 30+ small molecule therapeutics compounds against 18 different patients, including multi-region spatial heterogeneity sampling several individual tumours. Our data strong basis build upon GliExP incorporate combination-based oncology tandem with therapies as important murine (reduction replacement) triage experimental translation deliver rapid identification effective gliomas.</ns3:p>