The current treatment options for pancreatic ductal
adenocarcinoma fall exceedingly short of a cure, providing a sobering 5-year survival rate of only 5% for all patients, and the disease will be responsible for more than 37,000 deaths in the United States alone this year. These numbers continue to grow, and it was recently predicted that, within decades, pancreatic ductal
adenocarcinoma will become the second most lethal
cancer in this country. Beyond conventional oncologic-based
therapies, researchers are working hard, albeit with increasingly limited federal support, to develop multiple novel therapeutic options focusing primarily on targeting specific, disrupted core signaling pathways within
pancreatic cancer cells. In line with the history of medical oncology and medical paradigms, many pharmaceutical companies and large academic institutions have been focused on searching for compounds (biologic and chemicals) in an effort to find that unique "magic bullet" that will extend
pancreatic cancer patients' lives (e.g., K-ras inhibitors). This magic bullet has been difficult to find in a haystack full of molecular pathways and mutated genes because the challenge is defined by identifying a therapeutic window that kills the
tumor, yet spares the host. This therapeutic window has been hard to discover in the backdrop of the heterogeneous cell populations that make up a pancreatic
tumor together with a heterogeneous patient population that has multiple, undefined
tumor subtypes. Thus, to date, efforts have had limited success. Perhaps the best recent example of limited success is the discovery of the classic combination of
5-fluorouracil,
leucovorin,
irinotecan, and
oxaliplatin (
FOLFIRINOX), extending life by only 4 months when compared with
gemcitabine (note that this
drug combination does not directly target one single pathway or
pancreatic cancer subtype).