February 7, 2014

New direction for treating lung cancer

Targeting the production of molecules that promote tumor blood vessel development offers a new path for treating lung cancer.


Non-small cell lung cancer (NSCLC) accounts for about 85 percent of all lung cancer cases and has a high mortality rate, underscoring the need for new treatments. Ambra Pozzi, Ph.D., and colleagues report in the Jan. 15 issue of Cancer Research that activation of the protein PPAR-alpha represents a new avenue for treating NSCLC growth and progression.

The investigators previously showed that activation of PPAR-alpha reduces the expression of the P450 enzyme Cyp2c44 and its production of lipids that promote blood vessel development (angiogenesis). They now demonstrate in two mouse models that PPAR-alpha activators reduce primary and metastatic NSCLC growth and that these effects are associated with a reduction in Cyp2c44 expression and in the levels of its pro-angiogenic products.

The findings suggest that strategies to reduce Cyp2c expression and/or activity – including activation of PPAR-alpha – may offer new treatment options for NSCLC. One of the tested PPAR-alpha activators (bezafibrate) is already approved for lipidemia and could be quickly evaluated for its potential in lung cancer.

This research was supported by the VA Merit Review Award Program, the National Institutes of Health (CA162433, DK095761, DK083187, DK075594, DK069221, DK038226), and the NCI SPORE in Lung Cancer (CA090949).

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