Around 2015, Katherine Chiappinelli was investigating the mechanism behind a group of drugs approved to treat blood cancers—and showing promise against other cancers—when she made a puzzling discovery. Earlier studies had suggested that these drugs, known as DNA methyltransferase inhibitors (DNMTis), worked by triggering the expression of tumor suppressor genes. But Chiappinelli, then a postdoctoral fellow in Stephen Baylin’s lab at Johns Hopkins University, also saw an upregulation in genes involved in innate immunity.
It turned out that the drugs, which reduce the number of methyl groups that attach to and block transcription of certain segments of DNA, had removed the methylation suppressing expression of sequences within the genome that closely resemble and likely originated from retroviruses. These so-called endogenous retroviruses could then be transcribed into virus-like RNA that incited an immune response in cultured ovarian cancer cells. “The cell acts like it has a virus,” Chiappinelli, now at The ...
