When he walks into Dana-Farber Cancer Institute every day, medical oncologist Brian Wolpin, MD, MPH, isn’t just prepared to treat the patients who await him inside. As director of Dana-Farber’s Gastrointestinal Cancer Center and Hale Center for Pancreatic Cancer Research, he’s also constantly thinking about how new research could improve outcomes for patients with gastrointestinal cancer in the future.
“We are continually doing more science and more work so that we can improve the care for our patients,” he says. “That is why I show up every day. I want our group to treat patients today with the upmost compassion and informed by the latest science. At the same time, we want to ensure that the treatments we have to help patients tomorrow are even better than what we have available today.”
Earlier Detection is Key
Several of Wolpin’s recent research endeavors show great promise for patients with pancreatic cancer. An important part of improving treatment for the disease—which is normally diagnosed when it is in an advanced stage—is detecting it earlier on when it is easier to cure, Wolpin says.
“A major problem with pancreatic cancer is that 80 percent of the time the disease presents late in its course when it is already incurable,” he says. “To make a significant impact in treating this kind of cancer, we need to find it earlier.”
As part of a long-running collaboration with Matthew Vander Heiden, MD, PhD, an oncologist at Dana-Farber with a laboratory at the Massachusetts Institute of Technology, Wolpin and his colleagues determined that peripheral tissue wasting occurs early in the development of pancreatic cancer. As they recently reported in the journal Nature, the team detected reductions in muscle and fat tissue in mice before the onset of other signs of the disease—a potential warning sign—and early results suggests a similar process may occur in patients.
“We have multiple ongoing studies expanding upon this work,” Wolpin says. “In particular, we want to determine if the biology underlying wasting of peripheral tissues could be used for early detection, to indicate which people should be further evaluated for pancreatic cancer before it has spread to other areas of the body.”
Increasing Treatment Options Through DNA Sequencing
Once a person is diagnosed with pancreatic cancer, there are two primary chemotherapy regimens available for treatment. But together with fellow Dana-Farber oncologist Andrew Aguirre, MD, PhD, Wolpin and colleagues are working to identify new therapies based on the genetic information a patient inherits and that is present in their cancer. This work is designed to identify vulnerabilities in a patient’s cancer that can be exploited using new, tailored treatment approaches.
As part of an ongoing study, pancreatic cancer patients provided a blood sample and had their tumor biopsied to undergo sequencing of DNA and RNA. Their results, reported recently in the journal Cancer Discovery, showed that 18 percent of patients in their study had mutations that were inherited. Some of these mutations could be used to identify new, personalized therapies for these patients. Family members could also be offered testing to determine whether they had inherited the mutation that predisposes to pancreatic cancer, with important implications for cancer prevention and screening.
In addition, Wolpin and Aguirre discovered that some patients’ tumors had mutations that were not inherited and could be targeted with existing therapies approved for other cancers or were being evaluated in early stage clinical trials. In particular, defects in DNA repair were identified to be similar to those known to occur in a subset of breast and ovarian cancer. Furthermore, “targetable” mutations were identified in the 10 percent of patients who tumors did not possess a mutation in the KRAS gene.
The overall takeaway? DNA sequencing is feasible and could play an important role in improving treatment options for patients with pancreatic cancer. In a follow-up study, Wolpin and Aguirre are now also using biopsies of pancreatic tumors to grow 3D cultures called organoids.
“We can screen drugs against a patient’s tumor growing in the laboratory to look for new treatment options that weren’t obvious based upon the sequence data alone,” Wolpin says. “This provides another avenue to evaluate personalized treatment approaches for patients with pancreatic cancer.”
A Decade of Progress
During his decade at Dana-Farber, Wolpin has taken on leadership roles not only within the Institute, but on national and international committees dedicated to pancreatic cancer. He is chair of the NCI Pancreatic Cancer Detection Consortium Steering Committee, vice-chair of the NCI Pancreas Task Force, and principal investigator of the NCI PanScan Consortium.
“It is very gratifying to see a continually enlarging community of researchers thinking about pancreatic cancer and striving to make advances for our patients,” he says. “There really is a feeling of excitement that we are understanding the disease better, and that therapeutic improvements are around the corner originating from all the good science and hard work that people have been doing here at Dana-Farber, and around the world.”