Features | Partner Sites | Information | LinkXpress
Sign In
JIB
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING

Gene Fusions Make Some Pan-Negative Melanomas Sensitive to MEK Inhibitors

By BiotechDaily International staff writers
Posted on 16 Jan 2014
Image: Scanning electron micrograph of a melanoma cell. BRAF fusion genes in pan-negative melanomas may render them sensitive to MEK inhibitors (Photo courtesy of Vanderbilt University).
Image: Scanning electron micrograph of a melanoma cell. BRAF fusion genes in pan-negative melanomas may render them sensitive to MEK inhibitors (Photo courtesy of Vanderbilt University).
Cancer researchers have identified a class of fusion genes that drive melanoma metastasis in the 35% of these skin cancers that lack the previously known driver mutations.

According to senior author Dr. Jeffrey A. Sosman, professor of medicine at Vanderbilt University (Nashville, TN, USA) "About 35% of melanomas are, as of today, considered "pan-negative,” which means they are devoid of any previously known driver mutations in the genes BRAF, NRAS, KIT, GNAQ, and GNA11."

Dr. Sosman and his colleagues used a targeted next-generation sequencing (NGS) assay (FoundationOne) and targeted RNA sequencing to search for potential drug targets in a series of pan-negative melanoma specimens.

FoundationOne, the first clinical product from the biotech company Foundation Medicine (Cambridge, MA, USA), is the first commercially available targeted sequencing assay utilizing clinical grade next-generation sequencing (NGS) in routine cancer specimens. This test identifies all classes of genomic alterations (including copy number alterations, insertions, deletions, and rearrangements) in hundreds of cancer-related genes. It complements traditional cancer treatment-decision tools and often expands treatment options by matching each patient with targeted therapies that are relevant to the molecular changes in their tumor.

The investigators reported in the December 15, 2013, issue of the journal Clinical Cancer Research that they had found fusions between the bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 gene (PAPSS1) and the V-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) and between the BRAF gene and the tripartite motif-containing 24 gene (TRIM24).

Both classes of BRAF fusions activated the MAPK signaling pathway. The investigators treated fusion gene-bearing cells either with the BRAF inhibitor vemurafenib or with trametinib, an inhibitor of MEK, a protein in the MAPK signaling pathway. Results showed that signaling induced by the BRAF fusions was not responsive to vemurafenib but could be inhibited by trametinib, which implied that the fusions could make melanoma cells harboring them sensitive to MEK inhibitors.

"Performing a sophisticated analysis called targeted next-generation sequencing, it appears that about 8% of pan-negative melanomas have BRAF fusions," said Dr. Sosman. "Our results are important because they obviously suggest that there probably are other, as yet unidentified, molecular changes that make these melanomas susceptible to drugs that are available right now."

This study was funded in part by "Stand up to Cancer" (Pasadena, CA, USA), an organization that raises funds to accelerate the pace of cancer research in order to get new therapies to patients quickly and save lives now.

Related Links:
Vanderbilt University
Foundation Medicine
Stand up to Cancer


comments powered by Disqus

Channels

Drug Discovery

view channel

Ibuprofen May Restore Immune Function in Older Individuals

New research suggests that macrophages from the lungs of old mice respond differently to infections than those of young mice, and ibuprofen given to the mice reversed these changes. New research using lab mice suggests that the solution to more youthful immune function might already be a common over-the-counter pain reliever.... Read more

Therapeutics

view channel
Image: Hair follicle (blue) being attacked by T cells (green) (Photo courtesy of Christiano Lab/Columbia University Medical Center).

Hair Restoration Method Clones Patients’ Cells to Grow New Hair Follicles

Researchers have developed of a new hair restoration approach that uses a patient’s cells to grow new hair follicles. In addition, the [US] Food and Drugs Administration (FDA) recently approved a new drug... Read more

Lab Technologies

view channel
Image: Leica Microsystems launches the inverted research microscope platform Leica DMi8 (Photo courtesy of Leica Microsystems).

New Inverted Microscope Designed to Readily Adapt to Changing Research Demands

A new inverted microscope for biotech and other life science laboratories was designed to readily accommodate modifications and upgrades to allow it to keep current with changing research demands and interests.... Read more

Business

view channel

Partnership Established to Decode Bowel Disease

23andMe (Mountain View, CA,USA), a personal genetics company, is collaborating with Pfizer, Inc. (New York, NY, USA), in which the companies will seek to enroll 10,000 people with inflammatory bowel disease (IBD) in a research project designed to explore the genetic factors associated with the onset, progression, severity,... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.