A Swine Model of Glioblastoma

PROJECT SUMMARY GlioblastomaGBMis the most common and aggressive primary brain cancer with limited treatment optionsThe median survival for GBM patients is less thanmonths after diagnosisand tumors recur in overof patients after treatment with the standard of care consisting of surgical resectionradiationand chemotherapyMost preclinical research for GBM is conducted in rodentswhich have vastly different anatomy to humansparticularly regarding brain size and structuremaking surgery and imaging challengingRodents also differ drastically from humans in physiologymetabolismand geneticsand thereforeresponse to therapies in rodent preclinical GBM models is not always predictive of success in human clinical trialsMany GBM therapies are being actively investigated in clinical trialsAs of Decemberthe U SNational Library of Medicine has records forclinical trials for GBMof which have been completedsuspendedterminatedor withdrawnand yet none of these have improved the standard of care sinceA large animal preclinical GBM model that more closely resembles the human disease and is therapeutically predictive will improve GBM patient survival by ensuring the safety and efficacy of new therapies prior to human usePigs brains are much more similar to human in size and structure than rodentsmaking them ideal for testing therapiesperforming surgical techniquesand developing imaging proceduresTo generate a relevant large animal model of GBMwe propose to make the same genetic alterations in brain cells of live pigs that are most frequently mutated in human GBMThis will be the first large animal model to replicate the genetic landscape of human GBM in an immunocompetent pigwhich will allow the study of tumor developmentprogression and recurrence and enable the testing and refinement of promising targeted and immune therapies for GBMThis technology will also be highly adaptableallowing various combinations of oncogenes and tumor suppressor genes to be alteredallowing for rapid production of reliable swine models of multiple subtypes of human GBMThis swine model of GBM will allow the development and testing of novel imaging technologysurgical techniquesdevicestargeted drugsand immune therapies before or in parallel to clinical trialsimproving clinical success rates and increasing GBM patient survival PROJECT NARRATIVE Glioblastoma is the most common and most aggressive malignant primary brain tumor with a recurrence rate of overand ayear survival rate of less thandue to limited and ineffective treatment optionsThis proposal aims to develop a novel swine model of glioblastomaclosely resembling the human diseasewhich can be used to develop and test new drugs and immunotherapiesmethods of cancer detectionand surgical techniques to increase the survival rate for patients diagnosed with glioblastomaThis model will allow new therapies to be developed and evaluated pre clinically against the standard of care prior to human clinical trials in hopes of developing safer and more effective therapies for glioblastoma patients