The work is based on the viral mimicry ability in which cancer cells behave as if they were infected, thus activating the immune system to fight cancer as an infection.
Researchers have found silent ancient DNA elements buried in the genome that when “reactivated” can trigger this immune response, but a key enzyme used by cancer cells prevents this from happening, allowing survival.
By inhibiting this enzyme, cancer cells were more sensitive to new drug therapies that cause viral mimicry.
Humans have acquired a series of “silent” repeating elements in DNA for millions of years of evolution. These DNA relics have been found to be able to reactivate and stimulate the immune system under certain conditions.
The discovery of ADAR1 DNA adenosine deaminases that act on DNA…. immune response to cancer cells AD ADAR1 activity is enzymatic}.
Much knowledge has been gained about how the immune system interacts with cancer, leading to the development of new immunotherapy drugs, but there is still a large proportion of cancer patients who do not respond well to immunotherapy alone.
Epigenetic drugs have been shown to reactivate these repetitive DNA components and lead to the production of double-stranded RNA, which is also seen after viral infection. This “viral mimicry” leads to an antiviral response specifically directed against cancer cells in particular ancient repeating DNA elements as SINEs (Short Interspersed Nuclear Elements) that are usually quietly located in the genome having little effect on the host.
However, if activated by new epigenetic drugs, these SINES produce double-stranded RNA – a marker for infection – and can eventually be used by cells to elicit an innate immune response that can be used against cancer. But cancer cells are intelligent and have also evolved to avoid detection by the immune system even under conditions where ancient DNA sequences are activated.
Cancer cells have been found to produce more of the enzyme ADAR1, which works to disrupt the double-stranded RNA produced by ancient DNA. In this way ADAR1 prevents cancer cells from activating the immune system. Thus the deletion of ADAR1 from cancer cells makes them extremely vulnerable to epigenetic drugs that elicit the antiviral response.
SOURCE: University of Toronto. Nature “Epigenetic therapy induces transcription of inverted SINE and dependence on ADAR1″ .Oct. 2020.
