Targeting Melanoma With Chemical Snipers

Melanoma treatments may have a new target

(RxWiki News) Treating melanoma, the worst form of skin cancer, requires a creative approach. That’s because these tumors tend to ignore conventional treatment. Combining therapies may be the answer.

Scientists have discovered that two proteins – p53 and MDM4 – interact to produce melanoma.

It looks like a combination of therapies can break up this interaction and possibly improve the treatment of these aggressive cancers.

"Changes in a mole? Get checked out."

Agnieszka Gembarska, PhD, and Jean-Christophe Marine, PhD, researchers at the Center for the Biology of Disease at Vlaams Instituut voor Biotechnologie (VIB), Leuven, Belgium, led the investigation.

Dr. Marine said that the results not only improve the understanding of how melanoma develops, but also, “offers perspectives for optimizing the existing treatment strategies for melanomas.”

“The current treatment with BRAF inhibitors (vemurafenib) has positive effects on nearly 80 percent of the patients, but many of them relapse after a few months. We may have discovered a way of preventing this relapse,” Dr. Marine said in a press release.

Drs. Gembarska and Marine set out to understand the relationship between MDM4 and protein 53 (p53).

P53 is what’s called a tumor suppressor gene—meaning it works to keep cancer from forming. MDM4 interferes with p53 and keeps it from doing its vital job.

Researchers found that 65 percent of melanomas have higher levels of the MDM4 protein than regular cells.

By targeting MDM4 gene with a pharmaceutical, the research team was able to give p53 a way to do its job properly and squash melanoma growth.

Dr. Marine said, “The restoration of the p53 activity in the melanoma cells makes these cells more susceptible to chemotherapy and the BRAF inhibitors. In our research, we were able to identify MDM4 as a very promising target for treatment of melanoma, as part of a combination therapy.”

The BRAF inhibitor currently on the market for melanoma is called vemurafenib, brand name Zelboraf.

Clinical trials are the next step, and a new treatment standard may be years off.

This study was published in July in Nature Medicine.

Funding was provided by the Intramural Research Program of the US National Institutes of Health and the National Cancer Institute, the Association for International Cancer Research, the Melbourne Melanoma Project, the Victorian Cancer Agency and the Belgian Foundation against Cancer. No conflicts of interest were found.

Review Date: 
September 7, 2012