Test for identifying which cases of prostate cancer will become life threatening

Aug 20 2004

Karin Drotschmann, Ph.D., a researcher at Wake Forest University Baptist Medical Center, has won the “New Investigator Award” from the Department of Defense, Prostate Cancer Research Program, for her work to develop a test for identifying which cases of prostate cancer will become life threatening.

About 25 percent to 30 percent of prostate tumors reach an advanced, aggressive and life-threatening stage. Other prostate tumors are more slow-growing and may not require immediate treatment.

“Physicians don’t want to treat everyone with prostate cancer the same way,” says Drotschmann, an assistant professor of cancer biology. “But, the severity of prostate cancers differs considerably between patients, and there is currently no way to reliably predict which tumors will become life-threatening.”

Drotschmann’s goal is to identify markers that will allow doctors to predict disease progression.

The development of cancer is associated with alterations, or mutations in DNA, which carries genetic information and is found in the chromosomes of cells. Normal cells recognize and repair these mutations before they become permanent. Scientists believe that defects in repair mechanisms may result in the accumulation of mutations, which is the foundation for cancer development.

Drotschmann’s work focuses on a group of proteins – called mismatch repair proteins – that are part of one of the major repair mechanisms in every cell. Defects in mismatch repair proteins are linked to several types of cancer. Research has shown that mismatch repair proteins are also involved in cell death – killing cells that they are unable to repair. But, cancer cells are defective in this process and are incapable of dying on their own.

Drotschmann will study whether defects in mismatch proteins are involved when slow-growing prostate cancers become more aggressive and life-threatening. She will test the hypothesis that a decrease in mismatch repair proteins is associated with more aggressive cases of prostate cancer. Using sophisticated laboratory testing, she will study prostate cancer tumors to see if there are smaller amounts of mismatch repair proteins found in cells.

She hopes to eventually identify defects in genes that may be responsible for the mismatch repair proteins not working properly or decreasing in number. In addition, she will investigate how these defects in mismatch repair genes influence the accumulation of defects in other genes; this accumulation of genetic defects is the underlying principle of cancer development.

The ultimate goal is to improve treatment for a disease that kills about 30,000 men in the United States each year.

“We are using a novel approach that is focused on the molecular level and aimed at identifying factors that determine whether a prostate tumor will become aggressive and life-threatening during a patient’s lifetime,” she said.

Prostate cancer is the second-leading cause of cancer deaths among men in the United States. In 2004, over 230,000 men will be diagnosed with prostate cancer.

Drotschmann received $319,945 from the Department of Defense to conduct her research. Her work is also supported by the National Center Institute and the Comprehensive Cancer Center of Wake Forest University.