3D reconstructed pancreas: A model capturing the unique tumor microenvironment and stromal architecture of pancreatic cancer

AACR 2023 -- The prognosis for people with pancreatic cancer is poor, with an average 5-year survival rate of 10% and only 3% for those with metastatic illness. Pancreatic cancer patients have few therapeutic options, and innovative therapies are sorely needed to improve treatment of the disease. This is mainly due to the late diagnosis and partially due to the biology of the disease. It has been shown that human pancreatic tumors have an outer layer of stiff extracellular matrix (ECM) that functions as a physical barrier, preventing drugs from penetrating the tumor (Piersma, 2020). To address this with our model, we have incorporated a collagen capsule and have co-cultured pancreatic tumor cell lines with primary activated pancreatic stromal cells. We have created a 3D model of the pancreatic tumor microenvironment, the Reconstructed Pancreas (r-Pancreas), which is formulated to recapitulate the typical ECM of pancreatic tumors. We tested the response of BxPC-3, PANC-1 and Mia PaCa-2 pancreatic tumor cell lines embedded in this ECM to standard of care therapies. We demonstrated that gemcitabine was effective against pancreatic tumor cells cultured in r-Pancreas (IC50 = 0.4-0.8 �M), while 5-fluorouracil (5FU) was ineffective (IC50 not reached).