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New Research Provides Inroads Against Melanoma

Posted: August 17, 2009

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Up until now it was believed that the crucial process for skin cancer development is the unrestricted cell proliferation of the progenitor cells. Baccarini and colleagues now show in a mouse model that the Ras signalling pathway is coupled to the Raf-1 protein. Unexpectedly, the Raf-1 protein plays a key role in the differentiation process of the progenitor skin cells and not in the proliferation as previously assumed. Raf-1 ablation induced total regression of the epidermal tumors in mice. Mice without epidermal Raf-1 did not develop skin cancer, even though the Ras pathway was active.

Enzyme complex allows novel therapeutic strategies

The disruption of the normal pathway from progenitor cell to keratinocyte allows for the possibility of skin cancer development, as cancers such as melanoma frequently arise from these progenitor cells.

"We showed that Raf-1 builds an enzymatic complex with the protein Rok. This complex inhibits the differentiation to a skin cell and the way is clear for skin cancer development," Baccarini explains. She also identifies novel therapeutic avenues: "In the treatment of leukaemia substances are administered which stimulate cells to differentiate, combined with chemotherapy."

This combined therapy could be used for skin cancer treatment as well, if a substance is discovered that destroys the Raf-Rok complex and therefore enables differentiation. "The search for such substances up to the clinical application is a long road", Baccarini cautions. But with the discovery of this basic mechanism of skin cancer development Baccarini and colleagues provide the basis for research on novel therapeutic strategies.