Linda Vona-Davis, Ph.D., director of the Biomedical Master of Science in Health Sciences Program at West Virginia University, was surprised and delighted to see 65 of her colleagues at her recent presentation. Before the standing-room-only crowd, she discussed her latest research into how adipose-derived stem cells, which originate in fat, influence the activity of breast cancer cells.
Friday at noon has been a longstanding meeting of WVU Cancer Institute scientists, but the venue has recently taken on a new design with the hope of increasing collaboration across disciplines. With traditional programs set aside and discussions focused on broader thematic areas and “big problems” in oncology, Vona-Davis kick-started the semester in front of an animated, standing-room-only crowd.
Vona-Davis has diverse roles in the WVU School of Medicine. In addition to directing students pursuing the Biomedical Master of Science in Health Sciences degree in the Office of Research and Graduate Education, she lectures in cancer cell biology courses and explores the nexus of obesity, inflammation and breast cancer in her own laboratory.
Her presentation was the inaugural talk for the WVU Cancer Institute Science Exchange series, which will continue through the fall semester. The approach is intended to give a panoramic view of emerging cancer research, rather than close-up snapshots of data points.
In examining how breast cancer interacts with adipose-derived stem cells, Vona-Davis and her research team took a sample of the stem cells from breast fat, placed them in a collagen matrix to allow them to influence the microenvironment and then added tumor cells to the matrix. The model includes basal type triple negative breast cancer cells, the hardest to treat.
Even though the breast cancer cells in the study had shown signs of activity before—namely, by emitting two chemical signals associated with cancer progression—they seemed to grow quieter once they entered the collagen that the stem cells had vacated. Their emissions of the chemical signals stopped, suggesting that the crosstalk between breast cancer cells and the stem cells can cease once the stem cells “leave the room.”
The result indicates the possibility that stem cells from fat tissue may sequester aggressive tumors, at least temporarily. “It's an interesting observation,” says Vona-Davis. “Is this ‘site of sanctuary’ left behind by fat stem cells a place for tumors to rest or escape detection?”
Just as intercellular crosstalk can coax growth from breast cancer tumors, crosstalk among researchers can nurture investigations into those very tumors. When Vona-Davis’s presentation concluded, the question-and-answer session that followed included inquiries from faculty members and students, clinicians and basic scientists. They asked questions of her and of each other.
They also shared their initial impressions on directions the research could take based on their range of specialties, including microbiology, immunology and cell biology; pharmaceutical sciences, systems and policy; oncology in general; and breast cancer in particular.
What if Vona-Davis removed the deactivated cancer cells from the collagen? Would they revert to their active state? Would fat from other parts of the body yield different results entirely? What about patients’ leanness or obesity, or their exercise regimens? Would those variables matter? Would the quiet cancer cells be more resistant to radiation therapy?
Laura Gibson, Ph.D., senior associate vice president for Research and Graduate Education and deputy director of the WVU Cancer Institute, said, “The willingness of colleagues from so many directions to make time to come together and think about critical challenges in oncology in new ways is so exciting. All of our best science is derived from diverse teams, and to make true progress will require the creativity and dedication of everyone that was in that room. I was so appreciative of their engagement and loved their great ideas and questions.”
Vona-Davis hopes her research project will help lay the groundwork for disrupting fat–tumor interactions during future preclinical and clinical intervention studies.
“Given the high rates of obesity and breast cancer mortality in our Appalachian population, a systematic approach is needed to identify key underlying molecular signals that would have potential benefits in reducing the burden of breast cancer in women,” she said.
Richard Goldberg, M.D., who directs the WVU Cancer Institute, was also excited by the large attendance and many questions posed by the audience at his Science Exchange presentation, held on September 8. He discussed the efficacy of a class of drugs called PD-1 inhibitors that the Food and Drug Administration recently approved for managing cancers that exhibit defective mismatch repair.
When DNA divides and replicates, sometimes errors occur in the formation of the new strand of DNA. These errors are known as mismatches. Some tumors have a defect in their mismatch repair apparatus. This is analogous to defective “spell check” in a word-processing program. Mutations in those tumors’ DNA lead to abnormal proteins on the surface of their cells. Ordinarily a patient’s immune system does not recognize those abnormal proteins as dangerous and will not attack the tumor cells. Treatment with this new class of drugs allows the patient’s immune system to see the tumor cells as foreign invaders and target them for destruction.
Goldberg said, “This new approach gives us the keys to a whole new spectrum of treatments that have significantly fewer side effects than standard chemotherapy. I have seen some very satisfying responses in my patients who received treatment with one of the PD-1 inhibitors. These responses include complete tumor remissions that persist for years even after treatment ends.”
The fact that these treatments are FDA approved for any tumor with defective mismatch repair, regardless of its site of origin, is unprecedented.
WVU will hold the next session of the Science Exchange on October 20. Patrick Ma, M.D., co-leader of WVU’s Sara Crile Allen and James Frederick Allen Comprehensive Lung Cancer Program, will present on cancer immunotherapy.
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