Dr. Stefan Ambs: Increasing Diversity in Cancer Research: One Lab at a Time
, by CRCHD staff
As part of the feature series on “Increasing Diversity in Cancer Research,” we interviewed Dr. Stefan Ambs, an investigator at the NCI’s Center for Cancer Research, Laboratory of Human Carcinogenesis, who is using novel approaches to discover gene differences in the tumors of African American patients.
By examining the differences in tumor biology and tumor markers between African-Americans and whites, Stefan Ambs, Ph.D., M.P.H., a Senior Investigator in NCI’s Center for Cancer Research (CCR), Laboratory of Human Carcinogenesis, is attempting to unravel the biological complexities and survival differences that make up health disparities in African Americans.
Ambs has directed most of his attention to explaining biologically why African Americans have such poor survival rates in prostate and breast cancer, even when treatments are similar to whites. His research has already led to the discovery of an immune signature in tumors of African-American patients and demonstrated that nitric oxide synthase is a predictor of poor survival in breast cancer.
Breast Cancer Tumor Alterations
Ambs believes “race and ethnic differences in tumor biology manifest themselves because of inter-ethnic differences in environmental exposures or may arise from ancestry-related factors.”
Working on the premise that epigenetic alterations may affect tumor biology of African American breast cancer patients, Ambs with his colleague Atsushi Terunuma M.D., Ph.D. set out two years ago to focus on candidate gene loci. In experiments, which they performed in collaboration with Howard University researchers, the scientists found that DNA methylation in breast tumors was different in African Americans than whites. The differences appeared even more pronounced in women who were estrogen receptor negative or younger patients (less than age 50). Moreover, the scientists discovered a marker—CDH13—which was predictive of overall survival.
“Our research shows variations in immune function and differences in components of metabolism,” said Ambs. “All of these appear to contribute to disparities in African Americans.”
The Ambs lab also has an ongoing study evaluating the effect of stress exposure on tumor biology in African American breast cancer patients. Cancer epidemiology has linked stressful life events and discrimination to poor disease survival. According to Ambs, stress has been shown to influence tumor biology through two major pathways involving catecholamines and glucocorticoids. It appears that Tumor Associated Macrophages (TAM’s) interact with cancer cells “causing increased tumor angiogenesis and distant metastasis,” Ambs said. Ambs has found that breast tumors of African-American patients “contain a higher microvessel density and more TAMs than tumors from European-American patients.”
Prostate Cancer Tumor Differences
Ambs most recent “analysis of tumor markers have shown that biological differences exist in common cancers among patients of African, European, and Asian ancestry,” Ambs said. This “appears to particularly hold true in African American patients with prostate cancer.”
His research suggests that African American prostate cancer patients respond differently than whites to certain cancer therapies, particularly immune therapies. Most significant is the presence of an interferon signature that Ambs and his former postdoctoral fellow, Tiffany Wallace, Ph.D., (now a Program Director in CRCHD) found in many of the tumors from African American prostate cancer patients, suggesting that their immune response may be different. Ambs also found that most of the immune-related and metastasis-promoting genes were more highly expressed in tumors from African American patients than in those from European American patients.
“The differences in acquired mutations and immunobiology in prostate tumors may affect early disease detection and the response to therapy, and contribute to a distinct disease presentation of prostate cancer among men of African ancestry,” Ambs said.
Wallace explained, “the role of the immune system in regulating tumor initiation and progression is an extremely relevant topic in cancer research currently. Recent studies, including those from Dr. Ambs’ lab, indicate components of the immune response may be regulated differently in African American patients. These findings may help advance the understanding of biological contributors to cancer health disparities.”