January 30, 2013
Common Diabetes Drug Shows Promise As Lung Cancer Treatment
Watch the video "Diabetes Drug Could Hold Promise For Lung Cancer Patients"
Brett Smith for redOrbit.com - Your Universe OnlineScientists have been enthusiastic about the potential use of widely available diabetes drugs to treat various types of cancer. A new study from The Salk Institute for Biological Studies and the David Geffen UCLA School of Medicine suggests that these metabolism-affecting drugs can decrease the size of lung tumors in mice and increase their chances for survival.
According to the study, the diabetes drug phenformin may effectively treat 30 percent of patients with non-small cell lung cancer (NSCLC), a type of cancer with tumors that lack the LKB1 gene.
The LKB1 gene is crucial to every cell´s life cycle as it regulates metabolism by turning on an enzyme called AMPK when levels of the energy molecule ATP are running low within the cell. Previous research by some of the same researchers showed that cells without a normal copy of LKB1 do not activate the AMPK enzyme in response to low energy levels. This removal of a low-energy checkpoint for the cell is similar to removing the gas gauge on an automobile. The result of a defunct LKB1 gene is an out-of-control mutant cell that eventually runs out of cellular energy and undergoes apoptosis, or programmed cell death.
"The driving idea behind the research is knowing that AMPK serves as a sensor for low energy loss in cells and that LKB1-deficient cells lack the ability to activate AMPK and sense energy loss," said study co-author David Shackelford, an assistant professor at UCLA's David Geffen School of Medicine.
To examine the effects of the defective LKB1 gene in certain tumors, the California researchers looked to a class of drugs called biguanides, which lower cellular energy levels by inhibiting mitochondria, the cell´s power plant. While two of these drugs, known as metformin and phenformin, both inhibit mitochondrial activity, phenformin is about 50 times as potent as metformin.
In the experiment, the researchers tested phenformin´s effectiveness in genetically-engineered mice that lacked LKB1 and had advanced stage lung tumors. After three weeks of treatment, the team noted a modest reduction in the mice tumors.
The team then performed additional testing on mice in an earlier stage of disease and used cutting-edge imaging technologies similar to those used on lung cancer patients. The early-stage phenformin treatments resulted in increased survival rates and slower tumor progression in only those tumors that lack the LKB1 gene.
In an online video, lead researcher Reuben Shaw said that the study´s findings fit with an emerging attitude toward cancer treatment and research.
“The best way to effectively treat cancer is something called personalized medicine, where we understand what the genes that are mutated in each individual person´s tumors, what they do, and we come up with drug to fix that particular problem,” he said.
“We can (then) go in with razor-honed drugs that selectively target only that type of cancer with that type of genetic mutation.”
Although the phenformin treatment looks promising, the FDA actually took the drug off the market in 1978 due to a high risk of lactic acid buildup in diabetes patients with compromised kidney function. However, kidney issues may not affect cancer patients because the course of treatment would be much shorter compared to the years of drug treatment typically used to treat diabetes patients.
The study was recently published in the journal Cancer Cell.