Improper functioning of the mitochondria, a cell's source of energy, may help account for the fact that African-American men with prostate cancer respond poorly to the same conventional therapies provided to Caucasian-American men, according to research led by Dhyan Chandra, PhD, Associate Professor of Oncology in the Department of Pharmacology and Therapeutics at Roswell Park Cancer Institute (RPCI). The study was published online ahead of print in the British Journal of Cancer.
"In an earlier study, we provided the first evidence that African-American men possess reduced levels of mitochondrial genetic material in healthy prostate tissues, compared to Caucasian-American men. This new study highlights the importance of mitochondrial dysfunction as one of the main reasons for prostate cancer health disparities," says Dr. Chandra. "We conclude that the presence of severe mitochondrial dysfunction in African-American men with prostate cancer, compared with Caucasian men with the disease, would be one of the potential reasons for the increased cancer resistance to chemotherapy and the recurrence of disease."
Mitochondrial dysfunction is strongly linked to chemotherapeutic resistance leading to relapse of prostate cancer, but its effects can sometimes be overcome by treatment with the small molecule dichloroacetate. In prostate cancer cells from African-American men, dichloroacetate did not restore mitochondrial function to required levels.
This mitochondrial dysfunction within prostate cancer cells appears to make African-American men more resistant to current chemotherapy, putting them at greater risk for disease spread. The identification of new anticancer agents that would restore mitochondrial activity may result in better disease control, the researchers emphasize.
"These findings may provide an explanation for the higher incidence and mortality rates of prostate cancer among African-American men. African-American patients might get more positive outcomes after major restoration of mitochondrial function, which could improve the anticancer effects of therapy," adds Dr. Chandra.
"Although these findings are extremely insightful, more basic and clinical studies are needed to understand their impact in reaching our goal of eliminating the racial disparities in prostate cancer mortality," says co-author Willie Underwood, III, MD, MS, MPH, Associate Professor in the Department of Urology at Roswell Park.
This research was supported, in part, by grants from the National Cancer Institute (awards R01CA160685 and P30CA016056), American Cancer Society (RSG-12-214-01), Department of Defense (awards W81XWH-14-1-0013 and W81XWH-12-1-0406) and the Office of the Vice President for Research at the University of Georgia.
Article: Mitochondrial dysfunction-mediated apoptosis resistance associates with defective heat shock protein response in African-American men with prostate cancer, British Journal of Cancer, doi:10.1038/bjc.2016.88, published 26 April 2016.