Patient-derived organoids after neoadjuvant FOLFIRINOX predict therapy resistance in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma is an extreme lethal cancer with a poor treatment response to all the current chemotherapies. We generated a library of PDAC organoid lines from resected tumors, five from treatment-naive patients and five from patients who received neoadjuvant FOLFIRINOX (eight cycles). We assessed weather residual cancer cells in the tumor lesions of the patients treated with neoadjuvant FOLFIRINOX developed resistance to the treatment. Further we perfromed transcriptome analysis to investigate: 1- weather organoids recapitualting their corresponding tumor tissue 2- To investigate any modifications in the expression of the genes inflicted by FOLFIRINOX treatment. Overall design: We generated ten PDAC organoid lines, five from treatment-naive patients and five from patients who received neoadjuvant FOLFIRINOX (eight cycles). We first assessed the histological, genetic, and transcriptional characteristics of the organoids and their matched primary PDAC tissue. We evaluated the treatment response characteristics of the organoids to single agents of the FOLFIRINOX regimen —(i.e., 5-FU, irinotecan, and oxaliplatin). Finally, we used global mRNA-seq analyses to identify FOLFIRINOX resistance pathways.