BUSM Researchers Review Bromodomain Proteins as Possible Drug Target for Cancer and Inflammation

When proteins in control of gene expression are deregulated, they can lead to different kinds of cancer, including lymphoma, acute leukemia, midline carcinoma. The function of one class of such proteins, bromodomain and extraterminal (BET) proteins, was discovered by Gerald V. Denis, PhD, a faculty member in the Cancer Research Center and Department of Pharmacology and Experimental Therapeutics at Boston University School of Medicine (BUSM).

A new review article recently published in Nature Reviews Cancer, written by Denis, along with Anna Belkina, a PhD student in Molecular Medicine at BUSM, gives an overview of recent research regarding BET proteins, and presents the exciting possibility that they may be targets for future drug therapies aimed at various cancers.

Bromodomain proteins function by recruiting chromatin-regulating enzymes, which ultimately regulate gene expression. Previously, it was believed that these types of interactions were not ‘druggable’ targets. However, new research shows that there are small-molecules that can disrupt the interaction between the bromodomain and chromatin. These inhibitors have been shown to be very potent, and appear to be well tolerated. As a result of this discovery, there is now potential for a new array of therapeutics to be discovered, which could be used as combined anticancer and anti-inflammatory agents.

The article points out that these proteins work on several different pathways, so there may be unwanted systemic side effects. Future research will need to focus on creating agents that are selective for specific BET proteins, and minimizing undesirable effects. Some of these side effects might include “uncontrolled transcriptional depression of genes, altered hematopoiesis, immunosuppression or reactivation of latent viruses.”

“Nevertheless, the biology of these factors suggests that some co-morbidities such as cancer, obesity and inflammation are deeply linked in ways that researchers have not fully appreciated before, because certain diseases likely share the same set of gene expression regulators described here,” says Denis.

This review article was supported by grants from the American Cancer Society, Leukemia and Lymphoma Society and National Institutes of Health.

Submitted by Daniel S. Kirshenbaum, MD