Why is Pancreatic Cancer So Difficult to Treat?

Pancreatic cancer is seldom detected early enough for curative treatment to be performed – and even if it were, it would still be very difficult to vanquish.

The pancreas, a narrow, six-inch-long gland that makes digestive juices and hormones such as insulin, is tucked away deep inside the body behind the stomach, small intestine, liver, gallbladder, and spleen. When a tumor forms in the pancreas, it rarely causes noticeable symptoms until cancer cells have spread to other organs.

Pancreatic cancer cells.
Pancreatic cancer cells.

The only potentially curative treatment, as of now, is a complex surgery — called the “Whipple” operation — that removes parts of the pancreas and adjacent organs, which is only possible if the tumor is confined to the pancreas and not intertwined with major blood vessels, as is often the case. More than 80 percent of pancreatic tumors are deemed not removable by surgery when diagnosed.

Currently, there’s no reliable blood test or other screening method to detect early pancreatic cancer.

In addition to surgery, treatment for pancreatic cancer may include chemotherapy, radiation, and targeted drugs. But none of these modalities are very effective against these tumors, which are characteristically aggressive and defended by multiple levels of resistance.

For one thing, the tumors’ cells are genetically very unstable, allowing them to rapidly evolve defenses against treatment. The growth and spread of the vast majority of pancreatic cancers are driven by the extremely potent mutated KRAS cancer gene, for which no precision targeted drugs have yet been developed.

In addition, the tumor cells aren’t supplied by many blood vessels, and the tumor is embedded in a tough, fibrous matrix that acts as a barrier to chemotherapy drugs. And, while immunotherapies are proving highly effective for some patients with advanced cancers, they haven’t had much success in pancreatic cancer thus far.

Scientists, including those in Dana-Farber’s Pancreas and Biliary Tumor Center, believe that as they learn more about the biological underpinnings of pancreatic cancer and the factors that drive its resistance to treatments, there will eventually be improvements in outcomes for patients.

Learn more about treatment for pancreatic cancer at Dana-Farber.