Tag Archives: lung cancer

cancer

TGen finds clue to stop spread of lung cancer

Two cell surface receptors might be responsible for the most common form of lung cancer spreading to other parts of the body, according to a study led by the Translational Genomics Research Institute (TGen).

The hepatocyte growth factor receptor (HGFR/MET) and fibroblast growth factor-inducible 14 (FN14) are proteins associated with the potential spread of non-small cell lung cancer (NSCLC), according to the TGen study published online April 8 by the scientific journal Clinical & Experimental Metastasis.

NSCLC represents more than 85 percent of all lung cancers, which this year will kill an estimated 159,000 Americans, making it by far the leading cause of cancer-related death. It has a 5-year survival rate less than 10 percent.

The invasive and metastatic nature of NSCLC contributes to this high mortality rate, and so finding the cause of this potential to spread is key to helping patients survive.

Therapies targeting MET and FN14 are in clinical development, which could lead to treatments that could help halt or slow the spread of this lung cancer.

“As the metastatic phenotype is a major cause of lung cancer mortality, understanding and potentially targeting these pathways may reduce the high mortality rate in advanced lung cancer,” said Dr. Timothy Whitsett, an Assistant Professor in TGen’s Cancer and Cell Biology Division, and the study’s lead author.

Significantly, the TGen study found that MET and FN14 were elevated in metastatic tumors compared to primary lung tumors and suppression of MET activation or FN14 expression reduced tumor cell invasion.

“The elevation of these receptors in metastatic disease opens the possibility for therapeutic intervention,” said Dr. Nhan Tran, an Associate Professor in TGen’s Cancer and Cell Biology Division, and the study’s senior author.

Dr. Glen Weiss, Co-Unit Head of TGen’s Lung Cancer Research Laboratory and Director of Clinical Research at Cancer Treatment Centers of America at Western Regional Medical Center, said, “This study identifies some targets that already have drugs in clinical trials, and helps put them into context for what might be a rational drug development approach for the treatment of this deadly cancer.”

Other institutes that assisted with this study are: the University of Arizona; St. Joseph’s Hospital and Medical Center; and Humboldt Medical Specialists.

The study, FN14 expression correlates with MET in NSCLC and promotes MET-driven cell invasion, was funded by the National Institutes of Health, and grants from the St. Joseph’s Foundation and the American Lung Association.

cancer

TGen identifies key lung cancer enabler

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).