January 23rd, 2012

Melanoma Drug Accelerates Secondary Skin Cancers In Some Patients


Zelboraf® (vemurafenib) improves outcomes among patients with advanced melanoma that harbors a BRAF gene mutation, but also accelerates the development of squamous cell carcinoma in some patients. A study that explores the reasons for these secondary cancers was published in the New England Journal of Medicine. These findings may lead to treatment that preserves Zelboraf’s effectiveness against melanoma while reducing the risk of secondary skin cancers.

Of the more than one million new diagnoses of skin cancer each year, roughly 68,000 involve melanoma. More than 8,000 people die of melanoma each year in the United States. What makes melanoma so dangerous is that it is more likely than other types of skin cancer to spread (metastasize) to other parts of the body.

In order to provide more individualized and more effective cancer therapy, much research has been focused on determining specific pathways involved in cancer cell growth or survival. The BRAF gene is known to play a part in cell growth, and mutations in BRAF are common in several types of cancer. Approximately half of all late-stage melanomas carry a specific BRAF mutation known as V600E. Zelboraf blocks the function of the protein produced by this mutated gene and inhibits cell growth.

Patients treated with BRAF inhibitors such as Zelboraf have been reported to have high rates of secondary squamous cell skin cancers. To understand the reasons for this, researchers evaluated tumor samples from melanoma patients who had developed squamous cell carcinoma during treatment with Zelboraf.

  • Roughly 60 percent of the secondary squamous cell carcinomas had a mutation in the RAS gene. These RAS mutations are thought to be the result of prior skin damage from sun exposure. Zelboraf appears to accelerate the development of squamous cell carcinoma in skin cells with a preexisting RAS mutation.

Researchers are now exploring the use of a second type of drug in combination with Zelboraf; the goal is to preserve the effectiveness of Zelboraf against melanoma while also reducing the occurrence of secondary skin cancers.

Reference: Su F, Viros A, Milagre C et al. RAS mutations in cutaneous squamous-cell carcinomas in patients treated with BRAF inhibitors. New England Journal of Medicine. 2012;366:207-15.

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Tags: Melanoma, News, Stage III Melanoma, Stage IV Melanoma, Uncategorized