Research Highlight: Studying Tumor Suppressor Genes to Develop New Cancer Treatments

Chris Kemp is working to develop more effective, less toxic cancer treatments through genetic research. 

Cancer is a disease that, in one way another, impacts all of our lives. One in two men in the US are at risk of developing cancer, and one in four are at risk to die of cancer.  For women, the risk of developing cancer is one in three; the risk of dying from cancer is one in five.1 In 2013, nearly 1.7 million people in the US were diagnosed with cancer; over 580,000 died. More than 13 million people in this country are living with cancer .2

Cancer develops through a complex multistage process. Environmental damage over time increases the likelihood of genetic mutations, which can eventually cause cells to multiple continuously, leading to cancer. During this process, a number of genetic and environmental factors influence whether the cells affected by genetic mutations develop into cancer cells.

Researchers are working to understand the environmental causes of human cancer, the underlying mechanisms by which these environmental causes act, and the genetic factors that help determine how an individual reacts to various environmental exposures.

One such researcher is CEEH Environmental Mutagenesis & Carcinogenesis ARE (Area of Research Emphasis) Leader Dr. Christopher Kemp. Dr. Kemp runs a lab at the Fred Hutchinson Cancer Research Center. His work focuses on the genetic and biological basis of cancer and on developing more effective, less toxic cancer treatments.

Dr. Kemp uses functional genomics to discover the biological function of genes, and high-throughput screening (an automated process to test the biological activity of a large number of compounds) to systematically test large numbers of genes. He is searching for which genes cancer cells need in order to survive. These genes are weak points that could be attacked with drugs to selectively kill the cancer cells.

Recent research in Dr. Kemp’s lab focuses on a tumor suppressor gene called ARF. This gene has been found to suppress a devastating lung cancer, non-small-cell lung carcinoma (NSCLC). In 2013, Dr. Kemp led a study that found that ARF plays a role in suppressing multiple parts of NSCLC growth and progression. His team exposed genetically engineered mice that lacked the ARF gene (Arf -/-) to the cancer-causing chemical urethane. They found that the Arf -/- mice had shorter lives and higher morbidity from lung tumors than did control mice (Arf +/+ and Arf +/-) .3

The team’s findings suggest that the ARF gene functions as an early defensive response to lung tumors by creating a barrier against tumor growth and malignant progression.

Kemp’s team also used Arf -/- mice exposed to urethane to study the role of ARF in a deadly liver cancer, hepatic haemangiosarcoma. The findings suggest that lack of the ARF gene is one cause of this liver cancer. The ARF pathway, the series of actions among molecules in a cell that makes a new molecule or turns genes on or off, may be a new molecular target to treat patients with this deadly cancer .4

Chris Kemp’s research has convinced him that science is close to making big progress against cancer. He says, “I’m more optimistic than ever before.”
  1. http://www.cancer.org/cancer/cancerbasics/lifetime-probability-of-developing-or-dying-from-cancer
  2. http://seer.cancer.gov/statfacts/html/all.html
  3. Busch SE, Moser, RD, Gurley KE et al. ARF inhibits the growth and malignant progression of non-small-cell lung carcinoma. Oncogene (2013), 1-9.
  4. Busch SE, Gurley KE, Moser RD, Kemp CJ. ARF suppresses hepatic vascular neoplasia in a carcinogen-exposed murine model. J Pathol. 2012 Jul; 227(3): 298-305.

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