Verteporfin Blocks Growth of Deadly Eye Melanoma

Simultaneous mutations in two G-protein encoding genes that cause the overexpression of a carcinogenic protein have been linked to the development of uveal melanoma, a deadly cancer of the colored areas of the eye.

Uveal melanoma is a rare cancer that is usually treated by surgical removal of the eye. However, uveal melanoma can spread to the liver, in which case patients typically die within two to eight months after diagnosis.

Genome studies have shown that a mutation in either the GNAQ (guanine nucleotide binding protein, q polypeptide) or GNA11 (guanine nucleotide-binding protein subunit alpha-11) genes, which encode the proteins Gq or G11, respectively, are found in about 70% of uveal melanoma tumors.

In the current study, which was published in the May 29, 2014, online edition of the journal Cancer Cell, investigators at the University of California, San Diego (USA) revealed that that these mutations cause the G-proteins to become permanently activated, which results in overexpression of the Yes-associated protein (YAP). Overexpression of YAP protein induces uncontrolled cell growth and inhibits cell death, triggering cancer development. Furthermore, treatment of uveal melanoma tumors with the YAP inhibitor drug verteporfin blocked tumor growth of cells containing Gq/G11 mutations.

“The beauty of our study is its simplicity,” said senior author Dr. Kun-Liang Guan, professor of pharmacology at the University of California, San Diego. “The genetics of this cancer are very simple and our results have clear implications for therapeutic treatments for the disease. We have a cancer that is caused by a very simple genetic mechanism, and we have a drug that works on this mechanism. The clinical applications are very direct.”

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University of California, San Diego