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DMS researchers fight melanoma on many fronts

The summer sun makes gardeners and hikers think about skin cancer, but several DMS researchers are thinking about melanoma—the deadliest form of skin cancer—year-round.

"Melanoma is a frightening disease," says epidemiologist Linda Titus-Ernstoff, Ph.D., who presented the results of a study on melanoma risk factors at the Mediterranean Melanoma Conference in May. "Millimeter by millimeter, it is a very aggressive human tumor. At the present time, surgical removal of an early lesion offers the only certainty for a complete cure. To defeat this disease, we need to focus on potential causes . . . as well as prevention of precursors and early melanoma detection."

Titus-Ernstoff actually disagrees with the notion that sun exposure increases the tendency to develop moles, which can lead to skin cancer. She cites evidence from many studies that point to the true culprits: individual pigmentation characteristics and unusual sensitivity to the sun. She theorizes that there is a "constitutional susceptibility" for certain people to develop moles—even if they experience normal sun exposure.

Linda Titus-Ernstoff researches risk factors for the deadly cancer melanoma.
Photograph by Katrina Mitchell

Alterations: To understand this propensity, Titus-Ernstoff has investigated alterations of p16, a tumor-suppressor gene that, when it functions normally, prevents uncontrolled growth. She and a colleague were the first to show that p16 alterations can occur in benign moles.

They have started analyzing the risk factors for melanoma and so far have found strong associations between melanoma and atypical moles, as well as melanoma and benign moles. Until the work is completed, Titus- Ernstoff encourages people to practice self-screening. "My interest in the feasibility of selfscreening was born years ago," she says. "At that point, our data showed that only a minority of melanomas were first detected by a physician. Most were first noticed by a patient, spouse, friend, or family member."

Levels: While Titus-Ernstoff is looking at risk factors for melanoma, Dartmouth oncologist Christopher Tretter, M.D., is investigating new immunological treatments for the disease. Having identified improved survival rates in patients with high levels of melanoma-specific killer cells in their blood, Tretter is hoping to discover the key to enhancing this immune response in all patients who have melanoma.

He is focusing on dendritic cells, which play a central role in presenting cancer cells to the immune system. "Melanoma is not a passive bystander," Tretter explains. "It actively suppresses the immune system. The immune system will try to eradicate the tumor, but its response is inefficient because . . . dendritic cells in a cancer-bearing host are not working properly."

Tretter's work on dendritic cells builds in turn on 20 years of research by immunologist Marc Ernstoff, M.D. (who is married to Titus-Ernstoff). Ernstoff has studied how to stimulate immune system signalers to enhance their cancer-fighting activity.

Focus: He believes the focus at Dartmouth on multiagent therapy will help overcome traditional barriers to immunological treatment. "There are places all over the world that are exploring these approaches," he notes, but "only a handful of places [have] the breadth of research that focuses on all the different areas like we do."

Tretter says DHMC's growing reputation for novel tumor immunotherapy is leading to national and international patient referrals. This fact encourages him to push on with his research.

"What excites me about this is being able to think out of the box in tumor immunotherapy," Tretter says. "It's interesting to understand how these cells interact, and how tumors can inhibit their function. It is such a young field, and there is so much we can do in it."

Katrina Mitchell

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