TGen Researchers Discover Key Protein

TGEN RESEARCHERS DISCOVER KEY PROTEIN THAT HELPS PREVENT DESTRUCTION OF LUNG CANCER TUMORS

Researchers at the Translational Genomics Research Institute have discovered a protein that helps enable one of the most common and deadly types of cancer to survive radiation and drug treatments. Non-small cell lung cancer makes up about 85 percent of the nearly 160,000 Americans expected to die this year from lung cancer, which by far kills more patients than any other type of cancer, accounting for more than one in four cancer deaths in the U.S. annually. The five-year survival rate for advanced NSCLC is less than 10 percent.

In the absence of more effective targeted therapies, most lung cancer patients currently rely on platinum-derived chemotherapeutics, such as cisplatin, or radiation therapy. Previous TGen studies have shown that excessive activation of a cellular signaling mechanism known as TWEAK-Fn14 is linked to the survival and spread of cancer cells.

In a new study published in the scientific journal Molecular Cancer Research, TGen investigators found that a protein called Mci-1 helps enable TWEAK-Fn14, which in turn helps protect NSCLC tumors from being destroyed by radiation and drugs. Employing a drug called EU-5248, researchers using lung cancer cell lines found they could block Mci-1 function and halt the TWEAK-Fn14 cellular signaling mechanism.

"Our evidence shows that, if we can bypass these mechanisms, it will be more difficult for these lung cancer cells to evade therapies," says Dr. Nhan Tran, an associate professor in TGen’s Cancer and Cell Biology Division, and the study’s senior author.’¨’¨

The study concludes that additional research of Mcl-1 and TWEAK-Fn14 mechanism is needed, eventually leading to clinical trials and more effective treatments that could reduce lung cancer mortality. The drug, EU-5148, was provided by Eutropics Pharmaceuticals, based in Cambridge, Mass. Cancer Treatment Centers of America also contributed to this study, which was funded by the National Institutes of Health.

At top, Dr. Timothy Whitsett, an assistant professor in TGen’s Cancer and Cell Biology Division, and the study’s lead author, and Dr. Nhan Tran, an associate professor in TGen’s Cancer and Cell Biology Division, and the study’s senior author.

– Steve Yozwiak, TGen Senior Science Writer

PHOTOS COURTESY TGEN