Pancreatic cancer is certainly one of the truly rare cancers — a person has only about a one in 76 chance of developing it in his or her lifetime. But while its incidence is relatively uncommon — ranking around ninth among cancers — pancreatic cancer is one of the most deadly forms of the disease. With a 95 percent mortality rate, it rates as the fourth leading cause of cancer death in the United States.

James Posey, center, and his colleagues hope to develop a screening method to enable them to diagnose pancreatic cancer in its earlier stages. Posey says the key to this will be to define the patients who are at high risk for the disease.
Survival rates for pancreatic cancer are so poor often because it is not diagnosed until its later stages, and the few symptoms it exhibits usually do not appear early. In addition, doctors are not 100 percent certain of the risk factors that lead to the disease.

“We know of some risk factors, such as smoking, excessive alcohol use and obesity, but these don’t allow us to identify high-risk groups,” says James Posey, M.D., a UAB gastrointestinal oncologist and UAB Comprehensive Cancer Center scientist. “Our ability to diagnose pancreatic cancer in its early stages depends on a better understanding of the disease process so that we can identify high-risk groups and screen them for the disease.”

The Cancer Center is conducting a variety of clinical trials, many of which are connected with the center’s pancreatic cancer SPORE (Specialized Program of Research Excellence) grant. The prestigious grant — one of only three in the country — enables researchers and clinicians to speed the development of scientific breakthroughs into innovative treatments.

Several of these trials combine gemcitabine, a chemotherapy drug that is essentially the standard of care for treating pancreatic cancer, with other therapeutic agents. The goal is to find new agents that will make pancreatic cancer cells more sensitive to treatment and to examine the way in which the disease responds to each agent.

In one study, patients receive the drug Tarceva® for 10 days prior to surgery. Then, following their operation, they are given Tarceva in conjunction with gemcitabine. “We hope this will allow us to understand more about the pathway in pancreatic cancer that Tarceva disrupts and the factors in patients for which this therapy is most likely to provide benefit,” Posey says, adding that this applies to patients with more advanced disease.

In another study, gemcitabine is paired with a ras vaccine, which is designed to jump-start the body’s immune system to attack cells containing a mutated gene found to facilitate cancer. Another clinical trial teams gemcitabine with the chemotherapy agent Abraxane® for patients with metastatic disease. “We’ve seen a number of positive responses from the phase II trial and are encouraged that this might be an effective therapy for patients with less advanced disease, which is not the majority of our pancreatic cancer patients at UAB,” Posey says.

Improved imaging techniques also are offering physicians a new advantage, even though pancreatic cancer continues to be diagnosed most frequently in its later stages. Procedures such as CT scans and endoscopic ultrasounds allow doctors to better evaluate questionable or suspicious areas within the pancreas when symptoms do arise. With the slow increase in the incidence of pancreatic cancer over the past decade, clinicians and researchers hope to develop a screening method that could make a major impact on diagnosis.

The key, Posey says, will be to define the patients who are at high risk for the disease.

“Until we better understand the pathogenesis of pancreatic cancer and can begin to intervene at early steps in patients likely to develop the disease, it is going to be difficult to develop screening tools that would allow us to detect pancreatic cancer at an earlier stage,” Posey explains. “It’s a challenging arena, and we are slowly making progress. Hopefully that results in better benefits for the patient.”

Read more about other cancer research at UAB in the latest Crossroads magazine at www3.ccc.uab.edu/.