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

low energy loss in cells and that LKB1-deficient cells lack the ability to activate AMPK and sense energy loss," says David Shackelford, a postdoctoral researcher at Salk who spearheaded the study in Shaw's lab and is now an assistant professor at UCLA's David Geffen School of Medicine.

That led Shaw and his team to a class of drugs called biguanides, which lower cellular energy levels by attacking the power stations of the cell, called mitochondria. Metformin and phenformin both inhibit mitochondria; however, phenformin is nearly 50 times as potent as metformin. In the study, the researchers tested phenformin as a chemotherapy agent in genetically-engineered mice lacking LKB1 and which had advanced stage lung tumors. After three weeks of treatment, Shaw and his team saw a modest reduction in tumor burden in the mice.

Continuing the study between Salk and UCLA, Shaw and Shackelford coordinated teams in both locations to perform further testing on mice with earlier stage disease, using cutting-edge imaging technologies just like those used on lung cancer patients in the clinic. They found that early phenformin treatment causes increased survival and slower tumor progression in tumors lacking LKB1, but had no significant benefit for tumors with alterations in other lung cancer genes. This specificity in treatment fits with an emerging approach in cancer treatment nationwide, known as personalized medicine, in which the therapies for each patient are selected based on the genes altered in their tumors.

"This study is a proof-of-principle that drugs of this chemical type cause energy stress and lower ATP levels to where it kills LKB1-deficient cells without damaging normal, healthy cells," says Shaw, senior author of the study.

The Food and Drug Administration took phenformin off the market in 1978 due to a high risk of lactic acid buildup in patients with compromised kidney function, which is not uncommon among diabetics but less o
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Contact: Andy Hoang
AHoang@salk.edu
619-861-5811
Salk Institute
Source:Eurekalert  

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