Cancer :: True cancer-causing genes revealed by new technique

New research under the direction of Paul Khavari, MD, PhD, professor in the Program in Epithelial Biology at the Stanford University School of Medicine and chief of the dermatology service at the Veterans Affairs Palo Alto Healthcare System, shows a novel and more effective way of testing which mutations cause cancer and which are mere research distractions. The work is published in the June issue of Nature Genetics.

“If you have multiple suspects at the scene of a crime, you don’t know who committed the offense,” said Khavari. Without any way of differentiating the criminal from the bystander, researchers and drug companies spend time and money investigating all suspects. But Khavari and his colleagues have developed a technique that allows scientists to distinguish more quickly between possible perpetrators: they grew human skin cells on the skin of mice where the researchers could see the effects of mutations they induced.

“The surprise in this study was that what is perhaps the most famous mutation in this cancer didn’t cause melanoma,” Khavari said. A mutation in a gene for the protein B-Raf shows up in the majority of all melanoma cases. “This suggests that it must be doing something,” Khavari said. But when co-first authors graduate student Yakov Chudnovsky and postdoctoral scholar Amy Adams, MD, PhD, made that mutation in their melanoma model, the cells did not become cancerous.

Although these results came as a surprise, several cancer trials under way to target the B-Raf protein with chemotherapy haven’t been successful in treating melanoma. If people developing chemotherapy drugs had access to Khavari’s mouse model, they might have suspected that their trials would be in vain.

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