Lab technique IDs cancer-causing culprits
testing which mutations cause cancer and which are research
distractions has been discovered by scientists, who are hopeful
this application could become a standard in cancer diagnostics,
reports Wai Lang Chu.
The method appears to be a breakthrough for especially studying one of the hardest cancers to treat. Melanoma first appears as a mole or skin discoloration. The best way to beat the disease is to remove this early cancer before it spreads.
"Once it spreads, there are no therapies that are universally effective," said Paul Khavari, professor in the program in epithelial biology at the Stanford University School of Medicine.
Current approaches fail to realise that while some mutations do lead to cancer, others just tag along, frequently occurring but not driving the cancer to spread.
This latest technique involved researchers from the university growing human skin cells on the skin of mice where the researchers could see the effects of mutations they induced.
The process of fooling the human cells to grow on mice is considered extremely difficult. Normally the changes leading to cancer take up to 60 years to develop, which the team managed to squeeze into a number of days. This allows several different genes to be experimented on to test their ability to cause cancer
Central to this study was developing a way to induce mutations in the human skin cells and transplant them onto the mice. Previously, researchers studied melanoma in a petri dish where the cells don't behave like normal cancers. Although mice can develop melanoma, it is different than the human disease, thus is not the most ideal way of studying human cancer.
The key to this study was developing a way to induce mutations in the human skin cells and transplant them onto the mice. In the past, researchers studied melanoma in a lab dish where the cells don't behave like normal cancers. And although mice can develop melanoma, it is quite different than the human disease and is also not an ideal way of studying human cancer.
"The surprise in this study was 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, suggesting an active role," he added.
"But when fellow scientists on the team made that mutation in their melanoma model, the cells did not become cancerous," he added.
One unexpected result of the study found that a mutation that has been strongly linked with cancer mutation did not cause the melanoma. Khavari stated that a mutation in the gene for the protein B-Raf shows up in the majority of all melanoma cases.
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.
B-Raf turned out to be incapable of creating cancer, but another commonly mutated gene appeared to be a true criminal. Mutations in the gene that makes a protein called PI3K do cause melanoma in the mouse model.
In future work the team hopes to test additional mutations and develop similar models for other forms of human cancers.
