In a nation of sun-worshipers, melanoma is on the rise. Although doctors warn their patients to slather on sunscreen and seek cover in the shade, messages about sun safety still compete for the public's attention with magazine covers promoting that supposedly "healthy" tan look. While many other cancers are declining, melanoma – the deadliest form of skin cancer – is the fastest growing cancer in the U.S. Early melanoma is highly treatable, but there are limited therapies for people with advanced stages of the disease.
At The Wistar Institute, professor Meenhard Herlyn, D.V.M., is taking a broad-based approach to understanding melanoma in order to develop better treatments for people with the disease. Herlyn leads the largest melanoma research laboratory outside the National Institutes of Health, supported in part by a prestigious SPORE (Specialized Program of Research Excellence) federal grant, one of only three such awards nationwide.
"We are closer to a cure for melanoma than ever before because we have learned so much in the past few years," Herlyn says. "I'm optimistic that in the not-too-distant future we will be able to offer patients meaningful new treatment options."
An important thrust of Herlyn's research has been to develop artificial skin models in order to study melanoma. Tumors don't exist in isolation but rather interact with other surrounding cells and tissues – what scientists call the tumor microenvironment – and recent cancer research has focused on studying tumors in this dynamic context. Herlyn's skin models enable him to replicate the steps in melanoma progression. The development of melanoma is complex; while researchers know that UV light triggers melanoma – both through laboratory research, including earlier work by Herlyn, as well as statistical associations – the precise chain of events leading to tumor development has remained elusive.
In particular, Herlyn's group has been working to understand the chemical conversations carried on between skin cells. These chemical messages, or signaling pathways, keep cell division and proliferation orderly. But disruptions in these signals can lead to the kind of uncontrolled cell divisions seen in melanoma. In experiments, Herlyn has found that he can re-establish broken communication between cells, thus restoring control over this wayward cell division, a promising result that could point the way toward new targets for melanoma therapies.
Stem cells are an important tool in Herlyn's melanoma research. While much of the public discussion about stem cells has focused on their potential in repairing diseased or damaged tissue, stem cells are already becoming essential in cancer research like Herlyn's. Recent evidence has indicated that cancerous tumors may arise from deviant stem cells lingering in the body. These cancer stem cells seem to help maintain tumors through their remarkable powers of self-renewal. Herlyn is using federally approved stem-cell line to understand what role melanoma stem cells may plan in that disease.
Outside the laboratory, Herlyn devotes much energy to facilitating communication among melanoma researchers and reaching out to patient advocacy groups. He is president of the Society for Melanoma Research, which fosters collaborations among basic, translational, and clinical investigators. He also founded the Melanoma Research Congress, which brings together clinicians and researchers to discuss the latest developments in the field, and helped establish the Foundation for Melanoma Research, which raises awareness about melanoma and supports scientists conducting melanoma investigations.
In other melanoma research at Wistar, Herlyn's wife Dorothee Herlyn, D.V.M., also a professor at the Institute, has developed a novel vaccine approach to treating melanoma that showed marked effectiveness in a recent study. She and her colleagues used a small peptide found in approximately 70 percent of melanomas, but not in normal cells, to stimulate immune cells called killer T cells to attack the melanoma cells.
"In our experiments, we saw a strong cancer-killing immune response when killer T cells are stimulated with this peptide," says Dorothee Herlyn, who was senior author of the study, which appeared in the March 15, 2006, issue of Cancer Research.
A substantial proportion of melanoma patients, about 50 percent, have killer T cells able to recognize the peptide. Combining the prevalence of the peptide among melanoma patients with the number of patients whose immune cells are able to respond to the peptide suggests that a vaccine based on the peptide could treat approximately a third of all melanoma patients.
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