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- Posted Tuesday March 4, 2014
TGen identifies key protein that helps prevent lung cancer tumors from being destroyed
By eliminating Mcl-1, radiation and chemotherapies could be more effective in treating the most common and deadly of all cancers
PHOENIX, Ariz. - March 4, 2014 - Researchers at
the Translational Genomics Research Institute (TGen)
have discovered a protein, Mcl-1, that helps enable one of the most
common and deadly types of cancer to survive radiation and drug
treatments.
Non-small cell lung cancer (NSCLC) 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 1 in 4 cancer deaths in the U.S.
annually. The 5-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 laboratory study published in the scientific journal
Molecular Cancer Research, TGen investigators found that a
protein called Mcl-1 helps enable TWEAK-Fn14, which in turn helps
protect NSCLC tumors from being destroyed by radiation and
drugs.
"Our study demonstrates that the expression of Mcl-1 is necessary
to promote the TWEAK-mediated survival of NSCLC tumor cells," said
Dr. Timothy Whitsett, an Assistant Professor in TGen's Cancer and
Cell Biology Division, and the study's lead author. "By
deactivating Mcl-1, we believe we can give these lung cancer
patients a better response to standard therapy."
Employing a drug called EU-5148, laboratory researchers using lung
cancer cell lines found they could block Mcl-1 function and halt
the TWEAK-Fn14 cellular signaling mechanism.
"Inhibition of Mcl-1 function enhanced chemo- and
radio-sensitivity in NSCLC cells. The depletion of Mcl-1 … was
sufficient to abrogate the protective effects conferred on lung
tumor cells by TWEAK-Fn14 signaling," according to the study,
Mcl-1 Mediates TWEAK/Fn14-induced Non-small Cell Lung Cancer
Survival and Therapeutic Response, published online Jan. 27,
and awaiting print publication on April 14.
"This work positions both the TWEAK-Fn14 cellular pathway and the
Mcl-1 protein as potential therapeutic interventions," said Dr.
Nhan Tran, an Associate Professor in TGen's Cancer and Cell Biology
Division, and the study's senior author. "Our evidence shows that,
if we can bypass these mechanisms, it will be more difficult for
these lung cancer cells to evade therapies."
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 (Goodyear) also contributed to
this study.
The study was funded by the National Institutes of Health (NIH).
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About TGen
Translational Genomics Research Institute (TGen) is a Phoenix,
Arizona-based non-profit organization dedicated to conducting
groundbreaking research with life changing results. TGen is focused
on helping patients with cancer, neurological disorders and
diabetes, through cutting edge translational research (the process
of rapidly moving research towards patient benefit). TGen
physicians and scientists work to unravel the genetic components of
both common and rare complex diseases in adults and children.
Working with collaborators in the scientific and medical
communities literally worldwide, TGen makes a substantial
contribution to help our patients through efficiency and
effectiveness of the translational process. For more information,
visit:www.tgen.org.
Press Contact:
Steve Yozwiak
TGen Senior Science Writer
602-343-8704
[email protected]