The A.B. Hancock Jr. Memorial Laboratory for Cancer Research
Lawrence J. Marnett, Director
The A.B. Hancock Jr. Memorial Laboratory for Cancer Research focuses on the causes of cancer and on the development of novel agents for cancer prevention and treatment. The unifying theme of the Laboratory’s research is inflammation and its role in the development of cancer. Inflammation is a complex biological process that helps to fight off invading pathogens. Individuals who cannot mount an inflammatory response are at significantly increased risk of infection. However, chronic inflammation contributes to many diseases including heart disease and stroke, cancer, and arthritis.
There are many ways by which chronic inflammation can lead to cancer. Oxidants generated during the inflammatory response kill invading bacteria and viruses but can lead to DNA damage in surrounding tissue. This DNA damage can result in genetic mutations that can lead to the development of cancer. Furthermore, other reactive chemicals generated during oxidative damage to tissues lead to cellular changes that increase cell growth and decrease cell death. Finally, activated inflammatory cells release growth factors and other proteins that provide a strong stimulus for the development of cancer cells. Thus, chronic inflammation can be viewed as a “perfect storm” of molecular events that can lead to cancer development. Investigators in the Hancock Laboratory are using state-of-the-art techniques of chemistry and molecular biology to identify specific cellular changes caused by chronic inflammation and the biological consequences of these changes. The analytical methods developed in the Laboratory may ultimately be useful biomarkers that can help to detect cancer at an earlier stage of development.
Drugs that treat inflammation are broadly prescribed and have contributed significantly to improving human health. Because of the role of inflammation in cancer, anti-inflammatory drugs are being actively evaluated by researchers for their potential to prevent or treat the disease. The Hancock Laboratory has played an important role in these studies. A program is underway to design and synthesize the next generation of anti-inflammatory drugs that have increased potency and decreased side effects. In these efforts, Hancock Laboratory investigators are using structure-based design methods to maximize efficacy while minimizing toxicity.
Recently, the Hancock Laboratory has become heavily involved in high throughput screening for the identification of new therapeutic and preventive agents. Hancock Laboratory investigators are evaluating a large library of drug-like molecules in the High Throughput Screening Facility of the Vanderbilt Institute of Chemical Biology for their ability to inhibit the growth of tumor cells or induce their death. Thus, the Hancock Laboratory has become the focal point in the Vanderbilt-Ingram Cancer Center for anti-cancer drug discovery.