Chemotherapy and radiation often try to beat cancer in a blunt but effective way. They damage the DNA inside cancer cells so badly that the cells can no longer keep growing.
A new study points to one reason that plan can fail. Researchers found that MYC, a protein already known for pushing cancer growth, can move to broken DNA and help fix it, giving some tumors a way to survive treatment.
The finding is especially relevant for pancreatic cancer, where the five-year relative survival rate in the United States is 13.7% by Surveillance, Epidemiology, and End Results (SEER) data.
MYC’s double life
MYC is a transcription factor, which means it helps decide which genes are turned on inside a cell. In cancer, that can be dangerous because the same switchboard can push cells to grow, divide, and burn fuel at a frantic pace.
Rosalie Sears, senior author of the work at Oregon Health & Science University, and first author Gabriel Cohn, now at the University of Würzburg, focused on a strange contradiction. MYC can create stress and DNA damage, but it also seems to help tumors withstand that same damage–like a fire starter with a fire crew on speed dial.
The team found that MYC does more than sit in the control room of the cell. A modified version of the protein travels to damaged DNA and helps call in repair proteins. Sears called it a “non-canonical” role, meaning it is not the job scientists usually assign to MYC.
Why DNA damage matters
DNA is the cell’s instruction manual. When both strands of that manual snap in the same place, the injury is especially serious, because the cell has fewer easy ways to copy or patch the missing information.
That is partly why many cancer treatments try to cause this kind of damage. For many patients, that attack begins with an IV drip in a treatment room. In practical terms, the treatment tries to make the cell’s repair bill too large to pay.
Cancer is rarely that tidy, however. If a tumor repairs the breaks quickly enough, some cells can live through the attack and keep dividing. That is one way resistance can begin.
The chemical tag
The key detail is a process called phosphorylation. That simply means a tiny chemical tag is added to a protein, changing how it behaves.
In this case, the tag appears on one specific spot of MYC, and researchers call the tagged form pS62-MYC. Once tagged, MYC can reach DNA breaks and interact with BRCA1 and RAD51, two repair proteins that help rebuild damaged genetic material.
The study found that cells with this active form repaired DNA more efficiently and were more likely to survive stressful conditions.
Think of it like a badge that lets MYC enter the emergency zone. Without the badge, it stays closer to its usual job. With it, MYC becomes part of the cleanup crew.
Pancreatic cancer stands out
Pancreatic cancer is one of the hardest cancers to treat, for the most part because it is often found late and can resist therapy. U.S. survival statistics are a reminder of the stakes, with only about 13 out of 100 patients alive five years after diagnosis across all stages.
Cohn described the results as especially relevant for pancreatic cancer, where MYC activity is often high. The point is not that MYC explains every treatment failure, it is that it may give some tumor cells a survival tool at the exact moment therapy is trying to remove one.
A possible weakness
For decades, MYC has frustrated drug developers because it lacks the kind of easy docking spots many medicines use. It also touches many basic cell functions, so blocking all of MYC could carry risks for healthy tissue.
This new work narrows the question. Instead of shutting down everything MYC does, researchers may be able to focus on the repair-related form or the repair pathway it helps assemble. That is still a big “may,” but it is a more precise target than MYC as a whole.
A related 2024 Nature Medicine phase 1 trial tested OMO-103, a MYC inhibitor, in 22 people with advanced solid tumors and reported early signs of drug activity. Separately, an active early-phase study is examining OMO-103 in advanced pancreatic ductal adenocarcinoma by comparing tumor samples before and after drug exposure.
What happens next
The discovery does not replace chemotherapy, radiation, surgery, or newer targeted drugs. It gives scientists a clearer map of one escape route, and maps matter when the road is complicated.
The next step is to learn whether blocking this repair helper can make DNA-damaging treatments work better without causing too much harm to normal cells. That is the balance cancer medicine keeps chasing–hit the tumor harder, spare the patient as much as possible.
The official study has been published in Genes & Development.
