SEATTLE – A single molecule switches on metastasis, or spread, in pancreas cancers, reports new research led by scientists at Fred Hutchinson Cancer Research Center. The researchers predict that testing for this molecule, called RUNX3, could very soon help oncologists choose the most appropriate treatments based on the metastatic potential of each patient’s disease.
“We’re defining a readout that may help doctors in their approach to treatment of patients who have pancreatic cancer,” said Martin Whittle, Ph.D., a researcher in the lab of Sunil Hingorani, M.D., Ph.D., at Fred Hutch and first author on the paper, which was published online today in the journal Cell. The gene that we identified can be used to give some insight as to whether a patient’s tumor is more likely to grow locally or metastasize.”
RUNX3, the researchers found, controls the activation of numerous genes involved in metastasis in a mouse model, triggering cancer cells to migrate to other parts of the body and turning on genes that help those metastatic cells take root and thrive once they invade distant tissues.
“It’s extraordinary — it seems to control an entire metastatic program,” said Hingorani, the senior researcher on the study at Fred Hutch who specializes in pancreatic cancer. “RUNX3 serves to both expel the seed and prepare the soil.”
Pancreatic cancer has the highest metastatic drive of any malignancy. By the time they are diagnosed, most pancreas cancer patients already have either metastatic disease or tumors that have grown too much to be surgically removed. Even when patients’ tumors are contained, making them eligible for surgery or focused radiation, many of them end up dying of metastatic cancer anyway — because their apparently localized tumors had nevertheless already started spreading to other sites.
For this reason, oncologists often treat patients who have early-stage pancreas tumors with chemotherapy before surgery in the hopes of killing off any distant microscopic metastases and prolonging life. But in the time it takes for a few rounds of chemo, almost a third of surgically removable tumors grow too large to be eligible for surgery, a “devastating” outcome, said Hingorani, which slashes patients’ average survival time from two years for a removable tumor to less than 11 months for a non-operable tumor.
By predicting a tumor’s metastatic behavior, doctors could choose the type of treatment that gives their patients the best chance at the longest survival time, Hingorani said.
“I haven’t found a compelling explanation yet for the unusual metastatic drive of pancreas cancer, and certainly not one that would reconcile some of the paradoxes that exist both in the fundamental biology but also in treatment response in patients,” Hingorani said. “So for us, the thing that, on one hand, was worth the many years we spent studying it and why we finally felt ready to communicate it to the world, is that it helps us understand both the biology of the disease and ― most excitingly I think ― it might soon influence what we do in the clinic.”
Hingorani’s group already has studies underway to begin to translate their results into the clinic and learn more about how RUNX3 is regulated. “We’ve had such success in this mouse model in mimicking human PDA that we’re very hopeful that will translate well into humans,” Whittle said.
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At Fred Hutchinson Cancer Research Center, home to three Nobel laureates, interdisciplinary teams of world-renowned scientists seek new and innovative ways to prevent, diagnose and treat cancer, HIV/AIDS and other life-threatening diseases. Fred Hutch’s pioneering work in bone marrow transplantation led to the development of immunotherapy, which harnesses the power of the immune system to treat cancer with minimal side effects. An independent, nonprofit research institute based in Seattle, Fred Hutch houses the nation’s first and largest cancer prevention research program, as well as the clinical coordinating center of the Women’s Health Initiative and the international headquarters of the HIV Vaccine Trials Network. Private contributions are essential for enabling Fred Hutch scientists to explore novel research opportunities that lead to important medical breakthroughs.