Results obtained through analysis of genes in mice with liver tumors are providing some pieces to the puzzle of why some tumors spontaneously shrink—and how scientists could use gene therapy to force the same effect on other cancers.

College of Veterinary Medicine pathologist Dr. David Malarkey and collaborators at the National Institute of Environmental Health Sciences are using microarray technology with a mouse liver tumor model to provide the capability to quickly analyze expression levels for about 9,000 gene sequences. To date, Malarkey’s laboratory has identified about 400 genes in the mouse model. He’s hoping to identify critical genetic pathways involved in both cancer development and tumor regression.

Spontaneous regression of benign and malignant tumors is a rare but well-documented event in man and animals. Understanding the genetic mechanisms behind regression will offer insight into the biology of cancer evolution and what leads to tumor regression.” The information gained in Malarkey’s lab will be particularly valuable for understanding how environmental chemicals cause cancer. For example, chlordane, an insecticide used to kill termites in the United States until banned in 1985, causes liver cancer in mice and is suspected to cause cancer in humans. Studies have shown that when chlordane exposure is discontinued in mice with liver tumors, malignant and benign tumors completely regress. Preliminary results indicate that chlordane acts to cause mouse liver cancer partly by influencing pathways that favor liver cell growth and inhibit cell death. Malarkey explains, “Once the chlordane is removed, you ‘pull the plug’ on the cancer cells and they begin to die off and regress. Perhaps if we trigger these pathways in other cancers, we will develop more effective cancer treatments.

Contributing writer: Celeste Brogdon

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