Investigators at Michigan State University in East Lansing are finding new ways to treat cancer. For one, they are interested in novel molecular techniques that target cancer-causing genes. In particular, investigators are interested in a set of inhibiting drugs known as bromodomain inhibitors (BET inhibitors). The BET inhibitors work to block the expression of growth-promoting genes leading to slower tumor growth.
The BET inhibitors work to block the expression of growth-promoting genes leading to slower tumor growth. Researchers have studied the molecular mechanisms of BET inhibiting pathways in two separate studies: one research focused on the role of BET inhibitors in breast and lung cancer and the other examined the role of BET inhibitors on obesity-related cancers.
The first research study, led by Karen Liby a professor at the Department of Pharmacology & Toxicology, found that a BET inhibitor known as I-BET-762 slows the progression of existing lung and breast cancers through its interactions with an oncogene known as c-Myc. The c-Myc gene is known as the “master regulator” in that it regulates DNA transcription. The mutated version of c-Myc was found in many types of cancers. The mutation results in the abnormal functioning of this gene allowing cells to divide continuously without stopping, a striking hallmark of cancer.
"I-BET-762 works by targeting DNA so that this gene can't be expressed. It does this by inhibiting a number of important proteins — both in cancer and immune cells — ultimately reducing the number of cancer cells in mice by 80 percent," explains Liby.
BET inhibitors blocked the production of proteins that are necessary for cancer growth and survival. One such protein is known as pSTAT3 which in cancer cells it is overproduced providing a “protection” for cancerous cells to aid in tumor growth. BET inhibitors block the pSTAT3 activation, which is normally active in immune cells. In the study, the pSTAT3 levels were reduced by 50 percent in both immune and cancer cells.
In the second study, led by Jamie Bernard also a professor at the Department of Pharmacology & Toxicology, BET inhibitors were examined in precancerous cells, which are abnormal cells that had the potential to develop into cancer. This particular study focused on obesity-related cancers.
Obesity was seen to be a risk factor for multiple cancers including, pancreatic, breast, kidney, and colorectal cancers. The link between obesity and cancer is unknown however researchers believe may have something to do with changes in hormone levels, immune activity and presence of growth factors.
"Almost half a million of all new cancers have been linked to obesity. There is evidence that visceral fat and high-fat diets can increase cancer risk; and while current cancer treatments have helped to lower cancer mortality, the number of obesity-associated cancers continues to climb," explains Bernard. "We looked directly at the effect I-BET-762 had on human cells that could become tumorigenic but weren't quite yet." The results of the study were encouraging. "We found," he concludes, "that the drug prevented more than 50 percent of these cells from becoming cancerous."
It seems again that the gene c-Myc might be the reason for the success of I-BET-762. c-Myc is generated by visceral fat that encloses the body's organs, which is different from subcutaneous fat which is found below the skin. Visceral fat is known to be more harmful than subcutaneous fat.
The two studies were published in the journal of Cancer Prevention.