A new era: tumor microenvironment in chemoresistance of pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is a solid malignant tumor with an extremely poor prognosis. Gemcitabine (GEM)-based chemotherapy remains one of the most important treatment choices for PDAC. However, either as monotherapy or as a part of the combination chemotherapy, GEM achieved only limited success in improving the survival of patients with advanced PDAC, primarily due to GEM resistance. PDAC is characterized by an extensive desmoplasia in the tumor microenvironment (TME). Increasing evidence indicates that this fibrotic TME not only actively participates in the tumor growth and spread of PDAC but also contributes to the induction of GEM resistance. Here we review the current advances of how TME components are involved in the induction of GEM resistance.