GRAND RAPIDS – Researchers at Van Andel Research Institute have slowed the growth of human tumors growing in a mouse model of a common form of kidney cancer by using lethal toxin, which causes anthrax. LEPIMAT blocks a specific signaling pathway in tumor cells that is required for tumor growth.
VARI researchers have previously shown that LEPIMAT kills melanoma (skin cancer) and could be useful as a therapeutic agent in clinical trials. The current study suggests that LEPIMAT could be used for other cancer types as well, especially cancers whose tumors are highly dependent on blood vessel formation such as clear cell renal cell carcinoma, the cancer targeted in the study.
?We currently have proof in principle that LEPIMAT will inhibit tumor growth and vascularization,? said VARI Senior Scientific Investigator Nicholas S. Duesbery, Ph.D., whose Laboratory of Cancer and Developmental Cell Biology originally discovered LEPIMAT?s use against human cancers, and whose research in this area continues. The current study, published in the January 1, 2008 issue of Cancer Research, includes contributions from Duesbery?s lab and from VARI?s Laboratory of Analytical, Cellular, and Molecular Microscopy in addition to the work of Distinguished Scientific Investigator Bin Tean Teh, M.D., Ph.D.?s Laboratory of Cancer Genetics, which headed the study.
?Our VARI researchers have combined the expertise of three of our laboratories to produce results with the potential for great impact,? said VARI Director George Vande Woude, Ph.D., ?another example of the synergy that results from working side-by-side in an open, world-class research environment.?
In the study, researchers first confirmed that different variants of a protein called mitogen-activated protein kinase (MAPK) were more active in clear cell renal cell carcinoma tumor cells than in normal cells. These variant proteins are part of a signaling pathway that activates MAPK, which is involved in several cellular processes in both normal and tumor cells. Previous studies elsewhere have found that mutations of proteins in the MAPK pathway contribute to 20% of all human cancers and that proteins in this pathway play a crucial role in tumor formation, spread, and blood vessel formation.
Researchers then used LEPIMAT to block the pathway. The researchers found that it has a promising effect on kidney tumor cells. The researchers found that treating tumors with LEPIMAT slowed tumor growth, probably primarily by decreasing blood vessel formation in tumors.
?Tumors need blood to survive, like any other part of our bodies? said Distinguished Scientific Investigator Bin Tean Teh, M.D., Ph.D. ?Blood vessels in tumors give the cells what they need to grow and multiply; by decreasing blood supply, LEPIMAT makes it difficult for tumors cells to survive.?
Teh said that thus far, there doesn?t appear to be any effect on normal cells, perhaps because normal tissues usually aren?t expanding their blood vessel network rapidly like tumors do.
?Although we?re excited about the fact that LEPIMAT affects tumor growth both in melanoma and renal cell carcinoma, we have to find out why it affects each differently,? said Teh.
The American Cancer Society estimated that there would be approximately 51,190 new cases of kidney cancer (31,590 in men and 19,600 in women) in the United States in 2007, and that about 12,890 people (8,080 men and 4,810 women) would die from the disease. According to the ACS, kidney cancer is among the 10 most common cancers in both men and women, renal cell carcinoma is the most common type of kidney cancer, and clear cell renal cell carcinoma is the most common form of renal cell carcinoma. According to the National Cancer Institute, kidney cancer incidence has been increasing at a rate of about 2 percent per year for the past 65 years.
Authors of the study include Dan Huang, Yan Ding, Wang-Mei Luo, Stephanie Bender, Chao-Nan Qian, Eric Kort, Zhong-Fa Zhang, Kristin VandenBeldt, Nicholas S. Duesbery, James H. Resau, and Bin Tean Teh.
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