Expanding on previous findings, a group of Mayo researchers continue using discovery research in cells to find options for treating cancers. In their most recent paper, published in Molecular Cell, the team's research suggest that a drug used for breast cancer may be helpful in some types of prostate cancers.
"In the current study we show that in prostate cells, an overexpressed enzyme called DUB3 causes [drug] resistance due to the increased levels of a protein called BRD4," says senior author and Mayo Clinic molecular biologist Haojie Huang, Ph.D.
Bromodomain and extra-terminal domain inhibitors are drugs that prevent the action of BET proteins, an important task because these proteins help fuel cancer cells. BRD4 is a BET protein and enzymes like DUB3 fuel the protein's action. Dr. Huang explains that researchers already knew that DUB3 required the action of another group of enzymes called cyclin-dependent kinases, or CDKs.
In this paper, the scientists report that blocking CDK4 and CDK6 needed by the enzyme DUB3, decreases BRD4 protein levels in prostate cancer cells.
"Given that CDK4/6 inhibitor is already in clinical use, our findings could lead to immediate clinical trials for treatment of DUB3-overexpressed prostate cancer by combined use of BET and CDK4/6 inhibitors," says Dr. Huang.
In addition to Dr. Huang, other authors are: Xi Jin, M.D., Ph.D.; Yuqian Yan, Ph.D; Dejie Wang, Ph.D.; Donglin Ding, Ph.D.; Tao Ma; Zhenqing Ye, Ph.D.; Rafael Jimenez, M.D.; Liguo Wang, Ph.D.; and Heshui Wu, M.D.
Funding for this work was provided by the National Institutes of Health and the National Natural Science Foundation of China.