Newswise — ATLANTA—Dr. Ming-Hui Zou, director of the Center for Molecular & Translational Medicine and a Georgia Research Alliance Eminent Scholar in Molecular Medicine, has received a five-year, $2.3 million federal grant to study how to reduce tumor growth in lung cancer.

In the United States, more people die from lung cancer than any other type of cancer, according to the Centers for Disease Control and Prevention. In 2013, the most recent year for which statistics are available, 212,584 people were diagnosed with lung cancer and 156,176 people died from lung cancer.

As cancer develops, tumor cells release substances that promote the formation of new blood vessels, known as pro-angiogenic factors, by stimulating a response from endothelial cells, which line the inner walls of blood vessels. This leads to increased angiogenesis (the formation of new blood vessels), tumor growth and the spread of cancer.

Scientists have developed therapies that target vascular endothelial growth factor (VEGF), a potent angiogenic factor. However, the benefits of anti-VEGF therapies are often temporary because tumors become resistant to this therapy and start inducing new blood vessel formation with other pro-angiogenic factors. As a result, there’s an urgent need to find novel targets for treatment.

This grant from the National Cancer Institute of the National Institutes of Health will help Zou determine the molecular mechanism by which Liver Kinase B1 (LKB1), a tumor suppressor gene, suppresses transcriptional (gene) expression and activity of VEGF, NRP-1 and other pro-angiogenic factors, resulting in a reduction in tumor growth and a restriction in blood supply to tumors.

“The completion of this project will allow us to identify that enhancing LKB1 activity or expression is not only beneficial in suppressing cancer progression/metastasis but also in treating ischemic heart diseases,” Zou said.

The project has three aims. The first is to establish if LKB1 leads to decreased VEGF expression through impeding the activation of transcription, the first step of gene expression, in endothelial cells. The second aim is to establish if LKB1 suppresses NRP-1 and other non-VEGF growth factor-mediated angiogenesis in tumor cells. The third aim is to determine the contribution of LKB1 down-regulation of VEGF and NRP-1 within the vascular niche in mice.

An abstract of the grant, 1R01CA213022-01, is available at NIH's Project RePORTer website.

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