Pancreatic ductal adenocarcinoma (PDAC) is the fourth major cause of cancer related deaths in the U.S. Most patients with PDAC display an exceedingly poor prognosis with a mere 6 month median survival period mainly due to late diagnosis, the tendency of the cancer to spread early, and cancer cell resistance to radiotherapy or chemotherapy.

In a recent review for Cancer Biology and Therapy, professors Meir Preis and Murray Korc of the departments of medicine and pharmacology and toxicology at Dartmouth Hitchcock Medical Center analyzed current knowledge in the field to present evidence surrounding the key roles played by specific protein kinases in pancreatic cancer development. Their review, shedding light on the potential of kinase pathways as targets for intervention, may lead to novel methods in pancreatic cancer diagnosis and treatment.

PDAC is characterized by point mutations within genes affecting regulation of the cell cycle. These mutations alter cellular signaling pathways known as K-Yas, TGFß, Hedgehog, and Wnt pathways, which regulate processes such as cell growth, rapid cell division, migration and resistance to apoptosis-or genetically controlled cell death.  Consequently, a substantial amount of evidence supports that tyrosine kinase and serine/threonine kinase pathways play major roles in pancreatic cancer development.

Recently, these pathways have been targeted in new treatment therapies for patients with breast, lung, and skin cancer and produced dramatic results in raising survival rates and improving quality of life. Improvements in therapeutic treatment methods for PDAC, however, have yet to be made. “We need improved strategies to target specific pathways in pancreatic cancer,” said Korc.

The review written by the group of Dartmouth researchers provides an overview of the different kinase signaling pathways involved and affected by PDAC as well as data supporting targeting therapies available from clinical studies. The paper stresses the tremendous complexity and heterogeneity of the molecular and signaling front of pancreatic cancer.

It has recently been discerned that PDAC has an increased incidence in those older than 50-an indicator that it may pose a greater presence in the future. This contributes to the pressing call for more knowledge regarding the development of pancreatic tumors and the spread of cancer cells as well as for more effective novel therapies than those currently used.

A future goal of this research group is to “continue our work with transgenic models of pancreatic cancer in order to design novel diagnostic strategies for early cancer detection and therapeutic strategies that prolong patient survival,” said Korc.