I have dedicated my nearly 30-year career to the diagnosis and treatment of cancer. Pancreatic cancer has historically stood out as a disease for which diagnostic tools and therapeutic options have been sorely lacking.

Additionally, while it appears that between five and ten percent of pancreatic cancer cases arise in families with a genetic predisposition to the disease, only a handful of genes have been identified that are known to be linked to pancreatic cancer risk. The majority of the familial pancreatic cancer remains unexplained.

Thanks to my 2011 Innovative Grant from the Pancreatic Cancer Action Network, I have been able to focus on discovering which genes are involved in familial pancreatic cancer, and determining whether these altered genes can provide clues of how to best diagnose and treat the affected patients. This grant has allowed me to dedicate protected time and resources to this very important question.

I have the privilege of working with an outstanding collaborative team at Johns Hopkins University. Over the past six years, my laboratory has undertaken an ambitious project to establish cell lines from pancreatic cancer samples of patients with a family history of the disease. We now have nine cell lines, or cultures of cells that grow constantly in a dish, derived from patients with at least one primary relative (parent, child, or sibling) also diagnosed with pancreatic cancer. Moreover, we also have samples of normal DNA from the same patients.

Comparing the entire genome of pancreatic cancer cells to normal cells from the same patients will reveal the precise changes that have taken place leading to the development and progression of the tumor. As human genes are present in pairs (two copies of each gene), having a genetic proclivity to a disease usually entails being born with one faulty copy of a particular gene. Once the second copy becomes mutated or otherwise damaged, that is the tipping point that can lead to cancer.

My goal is to identify the genes that are mutated to cause familial pancreatic cancer in our nine cell lines. Knowledge of mutations that may put individuals at risk for pancreatic cancer can help inform decisions of how to monitor high-risk family members. It is important to provide comfort to family members who have not inherited the predisposition mutation that runs in a particular family, as well as to provide aggressive surveillance to those who have inherited it.

This experimental approach may also bring forward progress in treatment strategies. Recent evidence has shown that women with breast cancer caused by inherited mutations in the BRCA1 or BRCA2 gene respond particularly well to a certain type of drug. Therefore, the holy grail of this work is to identify a familial predisposition gene, and in future work, we hope to identify a drug that works specifically in patients who carry this genetic abnormality.

This project can only be accomplished because of my Innovative Grant from the Pancreatic Cancer Action Network and a fantastic collaborative team of colleagues.

Jim Eshleman, MD, PhD
Professor of Pathology and Professor of Oncology, Johns Hopkins University

Click here to learn about other recipients of Pancreatic Cancer Action Network grants