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A new tool to confront lung cancer
Date:6/19/2014

Only 15% of patients with squamous cell lung cancer the second most common lung cancer survive five years past diagnosis. Little is understood about how the deadly disease arises, preventing development of targeted therapies that could serve as a second line of defense once standard chemotherapy regimens fail.

Published online in Cell Reports on June 19, Huntsman Cancer Institute investigators report that misregulation of two genes, sox2 and lkb1, drives squamous cell lung cancer in mice. The discovery uncovers new treatment strategies, and provides a clinically relevant mouse model in which to test them.

"This is the most exciting thing we've done," said senior author Trudy Oliver, Ph.D., an assistant professor of oncological sciences at the University of Utah and Huntsman Cancer Institute investigator. "Now that we have a model it unleashes so many questions we can ask to gain a better understanding of the disease."

By definition, tumors are groups of cells that are out of control. As a result, they acquire mutations, only some of which drive properties such as excess growth and motility - that make cells cancerous. The trick for developing targeted therapies is to distinguish the "driver" from "passenger" mutations that are merely along for the ride.

Call it guilt by association, but Oliver's team honed in on drivers of squamous cell carcinoma (SCC) of the lung by poring through documented gene abnormalities found in human SCCs. Sox2 was designated a prime candidate based on its overexpression in 60-90% of SCCs, and a frequent early appearance during tumor formation, suggesting it could be an initiator of cancer. Tumor suppressor genes were also candidates, including Lkb1, which is mutated in 5-19% of SCCs.

While disruption of either gene alone failed to trigger cancer, combining overexpression of sox2 in the lung with loss of lkb1 led to frequent development of lung SCC in mice.

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Contact: Linda Aagard
Linda.Aagard@hci.utah.edu
801-587-7639
University of Utah Health Sciences
Source:Eurekalert  

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