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SPORE Project 3


Project 3 - GENE EXPRESSION PROFILING FOR PROGNOSIS AND THERAPEUTICS
                        Richard Myers, Ph.D. (HAIB) – Basic Co-Leader
                        Kenneth Ho-ming Yu, M.D. (CSHL) – Clinical Co-Leader
                        Sara Cooper, Ph.D. (HAIB) – Co-Investigator
                       Selwyn M. Vickers, M.D. (UAB) – Co-Investigator

Project 3 will develop precision targeted therapies based on genomics and patient-specific validation through evaluation with patient-derived pancreatic organoid cultures. Aim 1 will analyze PDAC tissue samples from patients spanning a large range of survival outcomes to optimize a gene expression signature for patient survival outcomes. Additionally, the mechanisms explaining association with survival for genes potentially involved in drug response will be determined, and an optimal signature of patient survival will be identified and linked to drug sensitivity. The drug sensitivity of patient-derived organoids and circulating tumorigenic and invasive cells will be determined in Aim 2, using both FDA-approved drugs and novel targeted therapies. RNA-sequencing of patient-derived pancreatic organoids and circulating tumorigenic and invasive cells will be used to generate expression and mutational signatures associated with drug response. In Aim 3, a clinical trial will be initiated wherein patient survival outcomes and a therapy regimen best suited to each arm of the trial are predicted based on molecular profiles of tumor biopsy material taken at diagnosis and circulating tumorigenic and invasive cell response to therapy. Fine needle aspiration (FNA)-derived tumor tissue will be used to establish organoid cultures for drug screening to direct therapy upon recurrence. This trial will determine whether patients with predicted poor survival have improved response to targeted therapy chosen based on genomic profiling.

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