DNA from Ancient Viruses Helps Many Cancers Grow

Cancer cells often find innovative ways to grow and thrive, using various biological tricks. A recent study has unveiled that many types of cancer exploit remnants of ancient viral DNA to fuel their growth. This groundbreaking research, published in Science Advances and funded partly by the National Institutes of Health, revealed that fragments of DNA left behind by ancient retroviruses act as genetic "on switches" for cancer cells.

The study identified one such viral DNA fragment, LTR10, which was particularly active in various cancers, including colorectal, lung, bile duct, and stomach cancers. LTR10 originated from a retrovirus that integrated its genetic material into the genomes of our ancestors over 30 million years ago. This viral DNA now activates several genes that help tumors grow and survive.

Dr. Edward Chuong from the University of Colorado Boulder's BioFrontiers Institute, who led the research, explained that the activity of these ancient viral fragments is influencing disease development today. While previous studies had shown the involvement of ancient viral DNA in individual cancers, this is the first study to demonstrate its widespread role across multiple cancer types.

The implications of this discovery are significant. Dr. Michael Weinreich of the National Cancer Institute, who was not involved in the study, emphasized that this research could lead to new cancer therapies. Specifically, scientists could develop methods to silence LTR10 and other similar viral sequences, potentially stopping tumor growth by cutting off one of its key survival mechanisms.

Retroviruses have been infecting human cells for millions of years, integrating their DNA into our genomes and leaving genetic "footprints" that are passed down through generations. It’s estimated that around 9% of the human genome is made up of ancient viral DNA. Most of this DNA is inactive, kept tightly folded and closed off from the rest of the genome. For years, it was believed that this viral DNA was simply junk, serving no purpose.

However, recent research has shown that some of these viral sequences have been "domesticated" by human cells and now play important roles in biological processes, including embryo development and cancer. For example, fragments of retroviral DNA can act as enhancers, turning on human genes necessary for cell growth or placental development. In cancer, these viral sequences can become active again, turning on genes that help cancer cells grow.

The study's analysis of The Cancer Genome Atlas revealed that most ancient viral DNA remains inactive in both healthy and cancerous tissues. However, LTR10 was found to be unusually active in several cancer types, including colorectal, lung, stomach, and prostate cancers. Further research showed that proteins associated with cancer, such as AP1 and MAPK, were responsible for "unfolding" LTR10 in cancer cells, allowing it to activate cancer-promoting genes.

Blocking these cancer-related proteins with specific drugs prevented LTR10 from acting as an enhancer, highlighting a potential new avenue for cancer therapy. Drugs like cobimetinib and trametinib, which are used to treat cancers with MAPK mutations, could be repurposed to inhibit LTR10 and its cancer-promoting effects.

The study took a closer look at LTR10 in colorectal cancer and found that it acts as an enhancer for multiple genes, including XRCC4, which helps cancer cells resist radiation therapy. In mouse models, deleting the LTR10 enhancer made radiation therapy more effective at slowing tumor growth, suggesting that future cancer treatments could target LTR10 to improve patient outcomes.

By targeting LTR10, researchers could potentially shut down several cancer-related genes at once, providing a more comprehensive approach to cancer treatment. As Dr. Weinreich noted, the impact of silencing enhancers like LTR10 could be much greater than targeting individual proteins, opening the door to new treatment strategies for various cancers.