Pancreatic Adenocarcinoma Therapeutics Targeting RTK and TGF Beta Receptor

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 (TGF beta R) 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/TGF beta R between pancreatic ductal adenocarcinoma (PDAC) and CAFs, as well as the RTKs/TGF beta R inhibitor-based clinical trials on pancreatic cancer are reviewed.

Automated summary

This article reviews the regulation of RTKs/TGF beta R between PDAC and CAFs, as well as the RTKs/TGF beta R inhibitor-based clinical trials on pancreatic cancer. It discusses the importance of considering the signaling of receptor tyrosine kinases and TGF beta receptors in overcoming the obstruction in the tumor microenvironment. The impact of receptor activation on cell cycle regulation, signal transduction pathways, and apoptotic sensitivity of tumor cells is also highlighted.