Colorectal cancer recurs in approximately 50% of people being treated for the disease. It is believed that recurrence is caused by a subset of cancer cells known as cancer stem cells, which are resistant to treatment and can multiply indefinitely. A team of researchers led by PM Cancer Centre Scientist Dr. Daniel De Carvalho has discovered a new therapeutic strategy that tricks cells into behaving like they are infected by viruses. This strategy could lead to more effective treatments that prevent the recurrence of colorectal cancer.
The researchers showed that treating colorectal cancer cells with the chemotherapy drug decitabine activates pathways that make the cells grow and proliferate more slowly and behave like they are infected with viruses. As a consequence of this, the cells are targeted and cleared by the immune system. Importantly, the researchers found that activating these pathways is effective against the hard-to-target colorectal cancer stem cells.
"By mimicking a viral infection, the immune system is tricked into seeing the cancer cells as an infection that needs to be destroyed. Our work demonstrates that viral mimicry is a viable anti-tumour strategy," says Dr. De Carvalho. Future studies will determine whether combining viral mimicry with cancer immunotherapy—a treatment that stimulates the immune system—provides more clinical benefits than either therapy alone.
This work was supported by the Cancer Research Society, the Canadian Cancer Society, the Natural Sciences and Engineering Research Council of Canada, the Ontario Institute for Cancer Research with funds from the province of Ontario, the University of Toronto McLaughlin Centre and The Princess Margaret Cancer Foundation.
DNA-demethylating agents target colorectal cancer cells by inducing viral mimicry by endogenous transcripts. Roulois D, Yau HL, Singhania R, Wang Y, Danesh A, Shen SY, Han H, Liang G, Jones PA, Pugh TJ, O'Brien C, De Carvalho DD. Cell. 2015 Aug 27. [Pubmed abstract]