Despite the improved overall survival rates in most cancers, pancreatic cancer remains one of the deadliest cancers in this decade. The rigid microenvironment, which majorly comprises cancer-associated fibroblasts (CAFs), plays an important role in the obstruction of pancreatic cancer therapy. To overcome this predicament, the signaling of receptor tyrosine kinases (RTKs) and TGF beta receptor (TGFβR) in both pancreatic cancer cell and supporting CAF should be considered as the therapeutic target. The activation of receptors has been reported to be aberrant to cell cycle regulation, and signal transduction pathways, such as growth-factor induced proliferation, and can also influence the apoptotic sensitivity of tumor cells. In this article, the regulation of RTKs/TGFβR between pancreatic ductal adenocarcinoma (PDAC) and CAFs, as well as the RTKs/TGFβR inhibitor-based clinical trials on pancreatic cancer are reviewed.
Keywords: TGF beta receptor; cancer- associated fibroblasts; pancreatic ductal adenocarcinoma; receptor tyrosine kinases.