Targeting Growth Factor Signaling Pathways in Pancreatic Cancer: Towards Inhibiting Chemoresistance

Abstract

Pancreatic cancer is one of the most deadly cancers, ranking amongst the top leading cause of cancer related deaths in developed countries. Features such as dense stroma microenvironment, abnormal signaling pathways, and genetic heterogeneity of the tumors contribute to its chemoresistant characteristics. Amongst these features, growth factors have been observed to play crucial roles in cancer cell survival, progression, and chemoresistance. Here we review the role of the individual growth factors in pancreatic cancer chemoresistance. Importantly, the interplay between the tumor microenvironment and chemoresistance is explored in the context of pivotal role played by growth factors. We further describe current and future potential therapeutic targeting of these factors.

Keywords: chemoresistance; chemotherapy; growth factors; pancreatic cancer; signaling pathways.

Figure 1

Examples of inhibition of the VEGFR and EGFR signaling pathways. (A) Inhibition of VEGFR signal transduction by sunitinib. After the entry of sunitinib into the cytoplasm, it competitively binds at the ATP site of VEGFR, consequently inhibiting the activation of the pathway. (B) Mechanism of action of Tyrosine kinase inhibitor, erlotinib. Erlotinib is a small molecule that acts as an ATP analogue and inhibits EGF signaling by binding to receptor tyrosine kinases (RTKs), and inhibits the activation of downstream signaling pathways.