By Scott Harris
As he sat by his mother’s bedside, watching her life slip away, Gregory L. Beatty, MD, PhD, director of the Clinical and Translational Research Program with the Penn Pancreatic Cancer Research Center, felt an emotion frustrating to many physicians: pure, utter helplessness.
“When we first got her diagnosis, it was like a shockwave,” recalled Beatty, an associate professor of Hematology-Oncology in the Perelman School of Medicine at the University of Pennsylvania. “As a son and a doctor, my thought was ‘how can I fix this?’ At that point, you realize how vulnerable we all are and how much we just don’t know.”
Beatty’s mother, Kathy, had glioblastoma multiforme, a rare and highly malignant cancer that affects the brain and spinal cord. Roughly 10,000 individuals in the United States die from glioblastoma every year according to the National Brain Tumor Society. Glioblastoma is so aggressive that the average survival time is only 15 months, or as little as three months if left untreated.
For Kathy Beatty, survival time was six weeks. The diagnosis came in December 2017. By mid-January, she was gone.
But before she died, her son made her a promise.
“I promised my mom, even though she probably couldn’t hear me, that I would try to make a difference,” he recalled.
Four years after her passing, Beatty’s promise, and his mother’s memory, are alive and well. Beatty and a team of Penn Medicine researchers recently published breakthrough study results in Cancer Immunology Research suggesting that the immune system may be fundamental to outcomes in glioblastoma. This finding furthers the possibility that one day immunotherapy might be used to treat glioblastoma, which is notoriously resistant to traditional treatment methods.
Beatty’s research also builds on years of research at Penn exploring cellular immunotherapies — similar to those developed at Penn Medicine and approved for certain blood cancers — as a potential better option for brain tumor treatment.
“Treatment options that are typically effective in treating other cancers — options like surgery, radiation, and chemotherapy — are not always enough to stop the spread of glioblastoma,” said Arati Desai, MD, an assistant professor of Clinical Medicine and Neurosurgery at Penn, who treated Kathy Beatty. “While Gregory's story is a sad one, it is inspiring to see the work he and his many Penn Medicine colleagues have done and are doing to combat this terrible disease.”
Pivoting Pancreatic Cancer Research to Brain Cancer Findings
Beatty was in an unusually strong position to fulfill his promise. As an established leader in pancreatic cancer research at the university, Beatty was able to pivot relatively easily to glioblastoma research using his existing knowledge and some of the tools involved in pancreas investigations.
“We took the techniques we had developed for pancreas cancer and applied those very similarly to glioblastoma,” he said.
Specifically, the study found greater numbers of T-cells, one of the immune system’s most potent weapons, in glioblastoma tumors that recurred after initial treatment compared with de novo or newly diagnosed tumors that had not yet been treated. The finding is important, Beatty and his colleagues wrote, because it showed that the body can and does engage its natural immune defenses against glioblastoma.
“Our study has important implications because of the suggestions that immunotherapy might have some activity in patients with relapsed tumors,” Beatty said. “We found that the relapsed tumors and the de novo tumors, immunologically speaking, were distinct.”
Additionally, Beatty and his colleagues found a potential target location for immunotherapy in glioblastoma tumors, with a higher numbers of T-cells massing in the areas surrounding the tumor’s blood vessels.
“Other studies had identified that T-cells seemed to hang around blood vessels in the glioblastoma tumors, and we certainly saw that too,” Beatty said.
The study was a collaborative effort, with a range of colleagues across Penn Medicine rallying around his personal quest. Other researchers involved were Donald O’Rourke, MD, director of Glioblastoma Translational Center of Excellence, and John Wherry, PhD, director of Penn’s Institute for Immunology and a co-leader of the Immunobiology Program at Abramson Cancer Center.
“I am so grateful to be a part of such an amazing team that united around my mom’s death – it really sparked our research,” Beatty said. “This is more than just a job for us; it is a passionate mission.”
According to the study authors, the findings open a whole new avenue of research that could guide scientists and physicians toward a better understanding of the immune response to glioblastoma — and ultimately, Beatty hopes, new treatments at the bedside.
“What we need to do now is really understand spatially where those T cells go, how they associate with different regions of the cancer, and try to understand how the tumors are changing under the kind of Darwinian selection pressure that T-cells can put on tumors. This knowledge will be key to getting a broader array of immunotherapy to work,” he said.
Even as Beatty’s quest continues, he reflected on the progress he and his colleagues have made since he sat helpless beside his mother as one of the world’s deadliest cancers ravaged her brain.
“I kept my promise,” Beatty said, “but this is only the first step. There is still so much to do.”