Lab technician Nicole Harrison and Stephen Hodi, MD, focus on their mission.
Spotlight on melanoma
Melanoma is a serious and growing problem. The ACS and other authorities estimate it is rising by 7—11 percent per year, faster than any other cancer in America, probably as a result of changing lifestyles that have increased sun exposure. About 55,100 cases will be diagnosed in the United States this year, and 7,910 deaths will occur; someone dies from advanced melanoma every hour.
The disease begins in the melanocytes, cells deep in the outer layer of skin, or epidermis, that manufacture the dark protective pigment called melanin. The risk of melanoma is highest among fair-skinned people — particularly those with many moles — who have little melanin and a history of severe sunburns. One part of the SPORE aims to learn more about specific risk factors and how they lead to different forms of the disease.
In several other SPORE projects, scientists are searching for abnormal chromosomes or genes in aggressive melanoma tumors. A telltale pattern of abnormal gene activity could be used as a "marker" to distinguish high-risk melanomas from those less likely to cause serious trouble, guiding physicians' treatment of patients.
DFCI researchers Lynda Chin, MD, and Todd Golub, MD, are hunting for differences in the genetic material of melanoma tumors and normal skin cells. Chin uses a technique developed with the Arthur and Rochelle Belfer Cancer Genomics Center at Dana-Farber to scan cells for large-scale changes in their chromosomal DNA. These alterations include broken or missing pieces of chromosomes, or bits of genetic material that have been duplicated abnormally.
"We hope these changes will either become markers — indicating a certain behavior of the tumor — or represent genes involved in the development of melanoma," says Chin. "If the latter, they could become targets for new drugs."
Golub, meanwhile, is searching for changes on a much smaller scale: Instead of big chunks of chromosomes, he's painstakingly measuring the activity of thousands of genes in melanocytes, comparing normal and malignant cells. If Golub and Chin find potential identifiers in their probes, they'll try to match them up. "These investigations are likely to fundamentally change our thinking about melanoma," says Kupper. "We may find markers that will predict the clinical course of a patient's tumor, even in very early disease."
Advanced melanoma is one of the most chemotherapy-resistant cancers, in part because it has somehow silenced many of the genes that can force damaged cells to self-destruct. The disease is then able to withstand therapies designed to trigger the celldeath pathways. David E. Fisher, MD, PhD, studies these pathways, as well as the genes that regulate them as a melanoma develops. From these and other insights, he is seeking molecular targets in melanoma cells that may be attacked by new generations of drugs.
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