INNV-24. Novel insights from and feasibility of functional precision medicine for glioblastoma and brain metastases patients through the Cancer Avatar Program at the CPMC Research Institute

Abstract Glioblastoma and brain metastases, the most common primary and overall brain tumors respectively, are characterized by rapid growth and diffusely infiltrative spread, come with the poorest prognoses, and have limited treatment options. Novel patient-specific treatment strategies are desperately needed for these cancers, as tumors with the same genetic alterations or molecular signatures may respond differently to the same therapeutics. The Brain Cancer Group within the Cancer Avatar Program at Sutter Health’s CPMC Research Institute in San Francisco collects and studies tumor samples from patients suffering from these malignancies. Here we highlight the Avatar process implemented for over 50 patients thus far as a guide to precision medicine in brain cancer. Tumor samples are processed on the same day as resection, with cells dissociated and implanted intracranially and subcutaneously into mice. Cells from the original tumor and dissociated from mouse brains or flanks at endpoint to form patient-derived xenograft (PDX) cells are both attempted to be grown in culture. Genetic testing is performed on the original patient tumor to determine any mutations/alterations, and inform the drugs chosen for high throughput drug screening (HTDS). Results from cells treated with single- or multi-agent cytotoxic and anti-migratory drugs are presented to the patient’s treatment team. We then create chemotherapy-resistant versions of patient cell lines whereby the cells are treated with the same chemotherapeutic agent the patient is treated with following resection to develop a mock-recurrent chemotherapy-resistant cell line. Repeat drug screening is performed and again presented to the care team. Drug screens have been completed in as few as 40 days from surgical resection. This process highlights the benefits of personalized medicine, feasibility despite the fast growth rate of these tumors, and the unique processes followed within the Cancer Avatar Program to provide patient-tailored drug options for when glioblastomas and metastases ultimately recur.