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Diabetes drug could hold promise for lung cancer patients
Date:1/29/2013

LA JOLLA, CA Ever since discovering a decade ago that a gene altered in lung cancer regulated an enzyme used in therapies against diabetes, Reuben Shaw has wondered if drugs originally designed to treat metabolic diseases could also work against cancer.

The growing evidence that cancer and metabolism are connected, emerging from a number of laboratories around the world over the past 10 years, has further fueled these hopes, though scientists are still working to identify what tumors might be most responsive and which drugs most useful.

Now, in a new study in the journal Cancer Cell, Shaw and a team of scientists at the Salk Institute for Biological Studies found that phenformin, a derivative of the widely-used diabetes drug metformin, decreased the size of lung tumors in mice and increased the animals' survival. The findings may give hope to the nearly 30 percent of patients with non-small cell lung cancer (NSCLC) whose tumors lack LKB1 (also called STK11).

The LKB1 gene turns on a metabolic enzyme called AMPK when energy levels of ATP, molecules that store the energy we need for just about everything we do, run low in cells. In a previous study, Shaw, an associate professor in Salk's Molecular and Cell Biology Laboratory and researcher in the Institute's new Helmsley Center for Genomic Medicine, demonstrated that cells lacking a normal copy of the LKB1 gene fail to activate AMPK in response to low energy levels. LKB1-dependent activation of AMPK serves as a low-energy checkpoint in the cell. Cells that lack LKB1 are unable to sense such metabolic stress and initiate the process to restore their ATP levels following a metabolic change. As a result, these LKB1-mutant cells run out of cellular energy and undergo apoptosis, or programmed cell death, whereas cells with intact LKB1 are alerted to the crisis and re-correct their metabolism.

"The driving idea behind the research is knowing that AMPK serves as a sensor for
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Contact: Andy Hoang
AHoang@salk.edu
619-861-5811
Salk Institute
Source:Eurekalert  

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