This mechanism has possible roles in evolution, drug resistance, as well as tumor formation in a significant proportion of breast and ovarian cancers.
Cancer cells often develop resistance to drugs, a major factor preventing the cure of many types of cancers. Current evidence suggests that cancers are caused by multiple genetic changes and that continued genetic change causes tumors to develop resistance to drug treatments.
The mechanism, discovered by the research team led by Derrick Gibbings, involves an ongoing war between a cellular degradation process called autophagy and ancient pathogens known as retrotransposons. Essentially, retrotransposons create mutations within the DNA and are responsible for a quarter of the genetic differences between two individuals.
“By mutating our DNA, retrotransposons have provided us with genes vital to important functions such as the formation of placenta. In fact, almost half our genome derives from retrotransposons. However, they can also create mutations that lead to drug resistance, cancers and other diseases,” says Gibbings, assistant professor of cellular and molecular medicine. “Mammals, including humans, could not have evolved without retrotransposons. But they’re both our enemy and our friend.”
The research team discovered that autophagy degrades retrotransposons and prevents them from creating new mutations in the genome. Autophagy is known to be insufficiently active in 35% to 70% of ovarian and breast cancer tumors. Gibbings’ team is currently following up on preliminary evidence that in breast cancer patients, retrotransposons become overactive and can affect the survival rate of these women.
“We now understand that retrotransposons have an impact on the creation and growth of tumors as well as the evolution of species. Our results suggest that autophagy helps buffer these processes,” says Gibbings. “This leads us to believe that by allowing autophagy to do its job, we may be able to slow tumors and their reappearance after chemotherapy through the use of some relatively benign drugs already being used to treat other medical conditions.”
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