Pancreatic cancer is the fourth leading cause of cancer-related deaths in United States. Despite advances in understandingcancer biology and therapeutics, this malignancy carries a grave prognosis with a poor overall survival rate. This is especiallytrue for patients with locally advanced and metastatic disease that are not amenable to surgical resection. Given advances inhuman genome sequencing and pharmacogenomics, we now better understand the complex genetic makeup of these tumorsand numerous gene mutations have been identified that could be potential targets for drug development. In this review, wediscuss two abstract (Abstracts #208 and #192) presented at the 2014 ASCO Gastrointestinal Cancers Symposium aboutpancreatic cancer genome sequencing and their implications for the future of this disease. We discuss what is known aboutthe genome of pancreatic tumors, including common mutations like KRAS, TP53 and SMAD4, as well as discovery ofadditional mutations. In particular, KRAS2 mutations in a subset of patients with pancreatic cancer are discussed. Whilelimited in size and clinical correlativity, these abstracts provide at least seven novel/targetable mutations and elucidatebiologic differences in tumors with wild type and mutant KRAS. These are important steps in understanding tumor biologyand genetic basis of pancreatic cancer to help develop targeted drug therapies in the fast approaching era of personalizedmedicine.
Muhammad Wasif Saif, Aditi Puri