• Michael Misialek, MD

What’s New in Pancreatic Cancer?

Pancreatic cancer represents 3% of cancers in the US, yet accounts for 7% of cancer deaths. The American Cancer Society estimates that in 2015 about 48,960 people will be diagnosed. More than 40,000 will die of pancreatic cancer. Unlike other cancers where advances in precision medicine have translated to improvements in diagnosis, treatment and prognosis, such progress has been slow with pancreatic cancer. Many factors likely contribute, including: an incomplete understanding of the causes, the lack of effective screening, limited success with current treatment regimens (chemotherapy, radiation) and a high mortality rate.

The Pathologist recently published a review of current concepts in pancreatic cancer. Some of the major topics are covered below.

Circulating tumor cells (CTCs) are emerging as a simple and cost effective method to monitor tumor response to treatment. Pancreatic cancer is one such area. The problem though has been the ability to obtain blood samples yielding high enough volume of CTCs. Recently it has been shown the sampling the portal vein directly through endoscopic ultrasound is a promising technique.

The dismal prognosis of pancreatic cancer is due in part to the advanced stage of presentation of most patients. Currently there are no effective screening tests or imaging studies to adequately detect and stage patients. That may soon change. Recently, new antibodies show promise for the molecular targeting of pancreatic cancer to provide more accurate information on staging, monitoring and treatment.

Pancreatic cancer is often thought of as a single disease. However, it is much more complex. New research suggests there are at least two molecular subtypes of cancer and two types of stroma (tumor microenvironment). Researchers are hopeful this new understanding will allow an individualized approach to pancreatic cancer by providing new treatment choices and prognostic information.

Effective screening techniques for pancreatic cancer have been elusive. One problem is deciding which pancreatic cysts need immediate intervention vs. those that can be safely followed. Researchers are beginning to understand which cysts are benign and which may progress to cancer.

Not only does late presentation contribute to poor outcomes in pancreatic cancer, but resistance to chemotherapy has also been a challenge. New research suggests that the epithelial to mesenchymal transition (EMT) that tumor cells undergo when they acquire metastatic potential, may also be important in chemoresistance. Blocking the EMT has shown increased chemosensitivity in preliminary studies. More studies are needed however.

Pancreatic cancer poses many challenges to effective treatment. It is able to survive low blood supply and oxygen in addition to being able to evade the body’s immune system. Here, immunotherapy has the potential to offer new promise. Researchers have shown that T cells engineered to recognize tumor cells have shown early promise in preclinical studies.

Epigenetics is also another exciting area of research. Recently it has been shown that small molecule inhibitors of histones (the support proteins for DNA) suppresses pancreatic cancer in mice. This approach may prove promising in many cancer types.

Novel therapies are also on the horizon. One particularly interesting strategy involves delivering drugs to tumors in small microbubbles. Then, using sound waves, the bubbles are burst open, releasing the drug exactly in the right location.

There is hope for optimism in the fight against pancreatic cancer. These new developments are bringing us closer to better treatment and survival for this deadly disease.

#pancreaticcancer #pathology #immunotherapy #precisionmedicine

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