Molecular and Biologic Characteristics of Pancreatic Cancer

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Pancreatic cancer is a genetically complex disease, with the average adenocarcinoma harboring 63 genetic changes. Although quite a bit has been learned over the last decade, there are no known driver mutations. KRAS mutations are almost ubiquitous. In addition, many tumor suppressor genes are mutated in pancreatic tumors (p53, p16, DPC4, SMAD4); however, developing targeted therapies against tumor suppressor mutations is very difficult.

It has been suggested that patients with a greater number of changes in tumor suppressor genes have poorer outcomes. Researchers are currently looking at prognostic subgroups based on these changes. Although targeting KRAS has not led to the discovery of effective therapies so far, recently the NCI began to focus on KRAS-mutated cancers to determine how to successfully target this pathway. It is hoped that new treatments will emerge from this work in the coming years.

Researchers are also exploring the predictive value of biomarkers such as SPARC and hENT1 for predicting outcomes with gemcitabine and nab-paclitaxel, and BRACA1/2 mutations for predicting outcomes with platinum-based therapy or PARP inhibitors.