Abstract D110: Same patient, different tumor. Does heterogeneity of pancreatic cancer matter? Differences in growth rates of patient-derived xenografts from individual patients

Abstract

Abstract Abstract Background Pancreatic cancer (PC) is one of the leading causes of cancer mortality and soon to be the second-leading cause of cancer death in the US by 2030. Patient derived xenografts (PDX) represent an opportunity to better understand the biology driving higher incidence and mortality. Racial disparities exist and Blacks have worse clinical outcomes than any other race. We hypothesize that the PDX tumors from the same patient will grow at differing rates including PDX development from patients of different races/ethnicities. Methods Under an IRB approved protocol, patients with the diagnosis of pancreatic adenocarcinoma (PDAC) were recruited for tissue donation. After surgical harvest of PC specimen, patient-derived xenograft (PDX) models were derived in NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. After initial passage from operation room, tumors from each individual patient were allowed to grow and subsequently divided and passed into 5 NSG mice and tumor growth rates were assessed by digital caliper. Patient race/ethnicity were de-identified as G and number of passages (p) from initial implantation were considered. Growth was assessed from 41 to 56 days. Coefficient of variation was attained and demonstrated the variability in growth values within each graft. Results PDX grafts (GXpX) were measured from 41 to 56 days. G1p5 and G2p1 were from non-Hispanic White patients and G3p3 was from a Black patient with PDAC. G1p5 grew an average of 0.25 mm per day and tumor size at 55 days after implantation were 1.0 cm, 1.4 cm, and 1.7 cm with a coefficient of variation of 20.98%. G2p1 grew an average of 0.17 mm per day and tumor sizes at 56 days were 0.7 cm and 1.3 cm with a coefficient of variation of 42.42%. G3p3 grew an average of 0.16 mm per day and tumor size at 41 days were 1.3 cm, 1.3 cm, and 0.7 cm with a coefficient of variation of 31.49%. The growth rate of mice implanted with patient tumor G2p1 demonstrated more growth variation than G3p3 and G1p5. Conclusion PDX from the same patient and different races exhibit differing growth rates over time. Each PDX should be considered as a unique tumor given its gross heterogeneity and possible genetic drift within the same tumor. Recommendations for PDX model use should include tumor measurements of each individual xenograft throughout time intervals throughout experiments especially when considering therapeutics. These important observations will leverage our understanding of much needed preclinical tumor models in PDAC and help improve our understanding of the biology of racial disparities in pancreatic cancer. Citation Format: Michael U Maduka, Patrick W Underwood, Andrea N Riner, Miles E Cameron, Jose G Trevino. Same patient, different tumor. Does heterogeneity of pancreatic cancer matter? Differences in growth rates of patient-derived xenografts from individual patients [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr D110.