Grants enable innovative approaches to pancreatic cancer treatment

McAllister investigates the potential of cancer immunotherapy against the disease, which has proven to be resistant to most therapies. In recent years, immune checkpoint blockade drugs have produced durable responses in some patients with a variety of cancers by unleashing an immune attack on tumors. However, pancreatic cancer has been resistant to the treatment in clinical trials.

“We’ll conduct mouse studies and a pilot study in humans looking at correlations between the composition of bacteria in the gut and both innate and adaptive immune responses and how they can promote or inhibit cancer,” McAllister says.

Gut bacteria, known collectively as the microbiome, are intimately connected to immune function, and scientists are just beginning to understand their impact on health and disease.

McAllister also has an appointment in Gastro-intestinal Medical Oncology and directs MD Anderson’s clinic for people at high risk for pancreatic cancer. Family history of pancreatic cancer and certain genetic mutations are among the factors that raise a person’s risk for the disease. The clinic’s goal is to detect pancreatic cancer earlier, when it’s most treatable.

Pancreatic cancer is curable with surgery in its earliest stages, but 90% of patients have advanced disease at diagnosis because it’s stealthy and hard to detect. Only about 6% of patients survive for five years.

Doubling survival time for pancreatic cancer patients

MD Anderson’s team of oncologists, surgeons and radiation oncologists has developed protocols for treating pancreatic cancer with chemotherapy and radiation before surgery, including locally advanced and borderline operable tumors. After more than 24 years of developing the approach via controlled clinical trials, the overall median survival of patients has nearly doubled – from 24 months during the 1990s to 43.4 months from 2010-14.

“We’ve had good experience at MD Anderson using higher doses of radiation in a subset of patients, with about 20 percent of those patients living five years or longer,” Taniguchi says.

The higher dose works for the minority of tumors that are not located right next to the patient’s small intestine, which is particularly vulnerable to radiation damage, according to Taniguchi.

His research focuses on a drug that inhibits the EGLN enzymes, which promote tissue healing. Taniguchi points out that the EGLN enzymes are found in abundance in normal tissue but not in cancer cells, which makes it less likely that this drug would help heal tumors.

“This grant is about improving our understanding of how these drugs work in preclinical studies before we move them into clinical trials so we can be more certain they will be safe in patients,” he says.

If EGLN inhibition successfully protects the small intestine, Taniguchi and colleagues will be able to increase the dose radiation to pancreatic tumors, which may improve outcomes in certain subsets of the cancer. 

Read about the latest progress in Making Cancer History® in the Cancer Frontline blog.