Project 2: Enhancing Efficacy of Gemcitabine Nanoparticles in Pancreatic PDX Models

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PROJECT SUMMARY/ABSTRACT: FULL PROJECT 2 Pancreatic Cancer (PCa) is a devastating disease for all affected. Presently, PCa is the 3rd leading cause of cancer-related death in the U.S. The five-year overall survival rate is a dismal 7.2%. While PCa has not be recorded as a cancer health disparity, the data is quite alarming, for example, Blacks experience a higher prevalence of compared to their Whites. Moreover, Black men and women have the lowest overall survival rates of PCa. Interestingly, while many cancers have demonstrated a reduction in incidence over a 5-year period (2008-2012), the incidence and number of deaths from PCa are projected to significantly increase among Blacks nationwide, further fingering PCa as a cancer health disparity. Additionally, although we have seen significant improvements in overall survival for prostate, breast, and colon/rectal cancer, PCa is projected to be the second leading cause of cancer deaths by 2030. Presently, there are no screening tests for PCa and early diagnosis is difficult because PCa often develops without any symptoms and indications are nonspecific. Thus there is a need, novel anticancer drug delivery that will enhance the efficacy of existing drugs, such as Gemcitabine for use to improve PCa patient outcomes. This collaborative study proposes to investigate critical barriers to PCa therapeutics and also define a more personalized therapeutic approach for underrepresented minority PCa patients. We will identify molecular charateristics that help differentiate molecular signature between pancreatic tumors among Blacks and Latinos which will allow for a more personalized approach to targeting PCa. We plan to design and develop stearoyl-linked-Gemcitabine with surface modified anti-EGFR antibody nanoparticles (GemEnps); evaluate GemEnps as a potential alternative chemotherapeutic agent in the treatment of PCa orthotopic PDX pancreatic animal models based on the similarities and differences in sequencing of pancreatic cancer genomes of Blacks, Latinos and Whites and translate knowledge of DNA changes to clinical tools for better management of Black and Latino with PCa.