While undergoing research on an anticancer drug targeting colorectal cancer cells, researchers at the Princess Margaret Cancer Centre found something surprising. The researchers discovered that the drug can actually trick the cancer stem cells into responding as if they had been infected with a virus, which in turn, limit the cancer cells' ability to multiply.
The findings were published academic journal Cell, and for Dr. Daniel De Carvalho, lead researcher on the project since its start in 2012, the finding is significant as colorectal cancer recurs in 50 percent of patients and is among the top three leading causes of cancer-related deaths. “We work with DNA methylation inhibitors, such as azacitidine and decitabine, both of which affect DNA methylation have already been approved by the FDA for use in myelodysplastic syndrome, a form of blood cancer,” Dr. De Carvalho said. “We are very interested in the ability of epigenetic agents to identify markers that are found mainly on cancer cells. Epigenetic drugs track down cells that have a lot of epigenetic markers, which are more likely to be cancer cells, whereas chemotherapy kills proliferating cells first, regardless of their epigenetic markers and regardless whether they are tumor or normal cells.”
The team found that these DNA methylation inhibitors make cancer cells more likely to attract immune cells, and in a phenomenon he calls ‘viral mimicry’, the drugs then trick the cancer cell to look like a cancer infected cell. “Combining epigenetic therapy with immunotherapy, where the brakes of the immune system are released, will probably improve patient response. We are currently starting trials to test this hypothesis.”
“By targeting colorectal cancer stem cells with a new anticancer agent, Dr. De Carvalho has succeeded in limiting the ability of these cells to grow and maintain tumors,” said Dr. Katie Wright, senior manager of Research Communications at the Canadian Cancer Society, Ontario Division. “This novel approach could potentially complement therapies for more effective treatment of other cancers.”
For 2016, Dr. De Carvalho is excited to continue research and hopes that this basic discovery will eventually improve patient care. “We are continuing this work in multiple fronts. First, by doing clinical trials to evaluate the synergistic effect of epigenetic inhibitors with immunotherapies,” he said. “We are also evaluating the effect of epigenetic therapy on the T cells. T cells are the ‘soldiers’ of the immune system. We want to know whether we can make these soldiers stronger by using epigenetic therapy.”