Mayo Clinic Researchers Block Cancer-Promoting Signals in Most Common Form of Lung Cancer

Thursday, February 02, 2006

Cancer researchers at Mayo Clinic in Jacksonville, Fla., used a therapeutic gold compound to block cancer-promoting signals between key proteins involved in the development of non-small cell lung cancer (NSCLC), the No. 1 cause of cancer deaths in the United States. If further research validates the Mayo findings, the novel strategy they devised could lead to promising new drug therapies that inhibit NSCLC — a significant advance for a widespread and common disease that typically does not respond well to existing therapies.

Significance of the Mayo Clinic Research
The Mayo Clinic report describing these findings appears in the Feb. 1 edition of Cancer Research (opens in a new window). In it, the Mayo team provides the first laboratory evidence supporting the concept of blocking "oncogenic" — cancer promoting — communication between a specific cellular protein known as Protein Kinase C iota (PKC1) and a second protein, Par6, that relays oncogenic signals from PKC1. Using a novel high-throughput drug screen, the research team identified a gold compound that disrupts the binding of PKC1 to Par6 and thereby blocks cancer-promoting signaling in NSCLC cells. The gold compound successfully halted the growth of human NSCLC cells in culture and NSCLC tumors in mice. NSCLC, one of two major forms of lung cancer, accounts for an estimated 80 percent of all lung cancers.

Dr. Alan P. Fields, Ph.D., director of Cancer Basic Science at Mayo Clinic Jacksonville and the Mayo Clinic Comprehensive Cancer Center researcher who led the team says this report is a key first step toward identifying a new therapy for NSCLC that targets PKC1.

"Our data provide proof of the concept that disrupting a key protein-to-protein interaction involved in cancer-promoting signals can be targeted and offer an effective treatment for NSCLC in our studies," Fields says. "This represents a novel approach in manipulating the signals that prompt tumor growth, and it's especially exciting because PKC has been the focus of research for so long."

PKC1 belongs to a family of proteins that were first implicated in cancer in the early 1980s, but a direct genetic link between them and human cancer has been lacking. Last fall, Fields' team reported the first genetic link between PKC1 and human cancer, demonstrating that PKC1 promotes cancer.

"Our current findings apply that basic discovery to identify a new PKC1-targeted agent that will hopefully improve treatment options for NSCLC," Fields says. "Though our recent results are promising, we don't know yet whether this approach will lead to improved therapy for lung cancer patients." However, Fields notes that the gold compound identified in his study is already approved for clinical use to treat rheumatoid arthritis, making it possible to begin early clinical testing soon in lung cancer patients.

About Lung Cancer
Lung cancer is the leading cause of cancer death in the United States, accounting for an estimated 160,440 deaths in 2004. Early stage NSCLC tumors are often treated with surgery and radiation therapy; and advanced cases are typically treated with combination chemotherapy. Despite aggressive treatment of early cases, the 5-year survival rate is only 14 percent.

Collaboration and Support
In addition to Fields, the Mayo Clinic research team included: Melody Stallings-Mann, Ph.D., Lee Jamieson, Roderick Regala, Ph.D., Capella Weems and Nicole Murray, Ph.D. Their work was supported by a grant from the Mayo Foundation.

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