December 2011

Chemical proteomic method reveals new target for treating head and neck cancers

MCP_coverAbout 600,000 new cases of head and neck squamous cell carcinomas are reported globally each year, making it the sixth-most-common form of cancer. The disease prognosis isn’t encouraging, with a 40 percent to 50 percent survival rate over five years. In a recent Molecular and Cellular Proteomics paper, a multinational research team described a potential new therapeutic target for the disease by using a chemical proteomics approach.

Stephan Feller of the Weatherall Institute of Molecular Medicine in the U.K. explains that head and neck cancers are the type that “arguably most devastates a patient’s life at the most basic personal levels.” He says because the cancers affect the head, they attack most of the senses, including taste, hearing and vision.

Feller and Bernhard Kuster of the Technical University in Munich led a team to investigate possible targets for therapeutic agents using a chemical proteomics approach. The approach probes the activities and interaction partners of proteins using small-molecule inhibitors. “Chemical probes allow purification and analysis of a relevant sub-proteome that is often not accessible to whole proteome expression profiling,” explains Kuster. The investigators specifically looked at kinases, a class of proteins that, according to Feller, is insufficiently explored for oncologic drug targets.

The investigators studied 146 kinases in 34 cell lines of head and neck squamous cell carcinoma using quantitative mass spectrometry and small interfering RNA assays for loss of function. Their analyses showed some of the previously known kinases involved in the disease, such as EGFR, but also revealed a novel drug target, EPHA2.  

The discovery of EPHA2 has opened up several new avenues of investigation, says Kuster. The researchers are now investigating how EPHA2 expression levels correlate with patient prognosis, and they are searching for small-molecule inhibitors against EPHA2 that can be used in studies using cell lines and animal models to find new drugs. Feller says that they also plan on using the same chemical proteomic method to work on other types of cancers.

Read the paper in Molecular & Cellular Proteomics.

Rajendrani Mukhopadhyay, Ph.D., ( is the senior science writer for ASBMB Today and technical editor for JBC. 

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