Inhibition of EZH2 May Benefit Many Melanoma Patients

March 4, 2016
Lauren Evoy Davis

A research team at University of California, Merced has identified a drug that could be effective in targeting melanoma cells.

A research team at University of California, Merced has identified a drug that could be effective in targeting melanoma cells. Professor Fabian V. Filipp, PhD, and his research team discovered a drug that suppresses the EZH2 (enhancer of zeste homolog 2) gene, which can silence other genes that suppress tumor generation.

This finding was first published in the journal Neoplasia on February 29, 2016. According to previous studies and continuing with this study, a dysregulation of EZH2 occurs in patients with melanoma-this has a negative effect on patient survival.

In many types of cancers, including hematologic malignancies such as lymphomas and leukemia, EZH2 is understood to exert its oncogenic effects through aberrant histone and DNA methylation, causing silencing of tumor suppressor genes. Recent studies have identified reversible H3K27me3 levels in response to aberrant EZH2 activity in melanoma, which demonstrates that it may be considered a drug target. The team's recent studies have shown that small molecule inhibitors of EZH2 could induce cell cycle arrest and apoptosis (cell death) of melanoma cells harboring somatic mutations of EZH2.

Researchers analyzed 471 cases of skin cutaneous melanoma (SKCM) in The Cancer Genome Atlas (TCGA) for mutations and amplifications of EZH2. Identified changes in target genes were validated by interrogation of microarray data from melanoma cells treated with the EZH2 inhibitor, GSK126. The changes in EZH2 were associated with an adverse prognosis in the TCGA dataset.

“We found that the EZH2 gene was activated in about every fifth melanoma genome,” said Dr. Filipp in a news release. “Our research indicates that inhibition of EZH2 is a promising therapeutic avenue for those patients. The next step will be to test the EZH2 inhibitor drug, known as GSK126, in clinical trials to positively confirm any therapeutic effects.”

Dr. Filipp's previous study  paved the way for the continuation of melanoma research and drug development. Using genomic data, they were able to identify a specific genetic mutation that drives the process that leads to melanoma. These efforts paved the way for their most recent work.

“In time, it’s possible that doctors will be able to scan a patient’s DNA and quickly identify both the specific type of cancer the person has developed and the best drugs to fight it,” said Dr. Filipp.