Lysyl oxidase family activity promotes resistance of pancreatic ductal adenocarcinoma to chemotherapy by limiting the intratumoral anticancer drug distribution

摘要: Solid tumors often display chemotherapy resistance. Pancreatic ductal adenocarcinoma (PDAC) is the archetype of resistant as current chemotherapies are inefficient. The tumor stroma and extracellular matrix (ECM) key contributors to PDAC aggressiveness limiting efficacy chemotherapy. Lysyl oxidase (LOX) family members mediate collagen cross-linking thus promote ECM stiffening. Our data demonstrate increased LOX, LOXL1, LOXL2 expression in PDAC, that level fibrillar collagen, which directly dependent LOX activity, an independent predictive biomarker adjuvant "Gemcitabine-based chemotherapy" benefit. Experimentally mice, activity through promotes chemoresistance. This effect seems be due decreased gemcitabine intra-tumoral diffusion. observation might explained by vessel size observed with activity. In conclusion, our support both a novel target improve well predict benefit PDAC. Beyond it possible targeting against different kinds solid tumors.