Identifying biomarkers of response to modified FOLFIRINOX regimens using patient derived xenograft mouse models of pancreatic ductal adenocarcinoma

Identifying biomarkers of response to modified FOLFIRINOX regimens using patient derived xenograft mouse models of pancreatic ductal adenocarcinoma Public Deposited

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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited effective therapies. FOLFIRINOX is a chemotherapeutic regimen for patients with metastatic disease that provides an unprecedented median overall survival of 11.1 months. However, significant toxicities necessitate dose reductions and limit the number of patients eligible for FOLFIRINOX treatment. I used patient derived xenograft (PDX) mouse models of PDAC to assess efficacy of modified regimens and determine if intra-tumoral heterogeneity plays a role in response. I also used RNA sequencing of PDX tumors to identify potential biomarkers of response. No significant differences in response to standard and modified FOLFIRINOX regimens were observed; however, intra-tumoral heterogeneity affected responses of one PDX tumor line to modified regimens. Biomarkers associated with differential responses could not be identified by RNA sequencing. RNA sequencing data confirmed previously identified PDAC subtypes, classical and basal-like.

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