Therapies to silence ‘endogenous retroviruses’ could make cancer treatments work better, according to new research.
These ancient hitchhikers were long considered inert or ‘junk’ DNA, defanged of any ability to do damage, but research published in Science Advances showed that when reawakened, they can play a critical role in helping cancer survive and thrive.
The study also suggested that silencing certain endogenous retroviruses could make cancer treatments work better.
“Our study shows that diseases today can be significantly influenced by these ancient viral infections that until recently very few researchers were paying attention to,” said senior author Edward Chuong, an assistant professor of molecular, cellular and developmental biology at the University of Colorado Boulder’s Bio Frontiers Institute.
Studies show that about 8% of the human genome is made up of endogenous retroviruses that slipped into the cells of our evolutionary ancestors, coaxing their hosts to copy and carry their genetic material. Over time, they infiltrated sperm, eggs and embryos, baking their DNA like a fossil record into generations to come.
Even though they can no longer produce functional viruses, Professor Chuong’s own research has shown that endogenous retroviruses can act as “switches” that turn on nearby genes.
Some have contributed to the development of the placenta, a critical milestone in human evolution, as well as our immune response to modern-day viruses like COVID.
“There’s been a lot of work showing these endogenous retroviruses can be domesticated for our benefit, but not a lot showing how they might hurt us,” he said.
To explore their role in cancer, Chuong and Atma Ivancevic, a research associate in his lab, analysed genomic data from 21 human cancer types from publicly available datasets.
They found that a specific lineage of endogenous retrovirus known as LTR10, which infected some primates about 30 million years ago, showed surprisingly high levels of activity in several types of cancer, including lung and colon cancer. Further analysis of tumours from dozens of colorectal cancer patients revealed that LTR10 was active in about a third of them.
When the team used the CRISPR gene editing tool to snip out or silence sequences where it was present, they discovered that critical genes known to promote cancer development and growth also went dark.
“We saw that when you silence this retrovirus in cancer cells, it turns off nearby gene expression,” Ms Ivancevic said.
Experiments in mice yielded similar results: when an LTR10 “switch” was removed from tumour cells, key cancer-promoting genes, including one called XRCC4, were also switched off, making treatments to shrink tumours more effective.
“We know that cancer cells express a lot of genes that are not supposed to be on, but no one really knows what is turning them on. It turns out many of the switches turning them on are derived from these ancient viruses,” Professor Chuong said.