For years, scientists have known that the MYC protein acts as a fuel source for tumor growth. However, new research reveals that MYC does more than just drive expansion—it actively protects cancer cells from the exceptionally treatments designed to kill them. By repairing damaged DNA, MYC helps some of the deadliest cancers survive chemotherapy and radiation.
Key Takeaways
- Dual Role: MYC doesn’t just promote cell growth; it also functions as a DNA repair mechanism.
- Treatment Resistance: By fixing DNA breaks, MYC allows tumor cells to recover from chemotherapy and radiation.
- Pancreatic Cancer: This mechanism is particularly aggressive in pancreatic cancer, where MYC activity is often very high.
- New Targets: The discovery of MYC’s role in DNA repair provides a new strategy for targeting a protein previously considered “undruggable.”
Beyond Growth: MYC’s Unexpected Role in DNA Repair
The protein MYC is abnormally active in most human cancers. Traditionally, researchers understood MYC’s role as a genetic switch inside a cell’s nucleus, turning on genes that drive metabolism and growth. But a study published in Genes & Development has uncovered a “non-canonical,” or nontraditional, function of the protein.
When DNA is damaged—whether through the stress of rapid tumor growth or as a result of medical treatment—a modified version of MYC moves directly to the site of the damage. Once there, it helps gather the necessary proteins to repair the break.
“Our work shows that MYC isn’t just helping cancer cells grow — it’s also helping them survive some of the very treatments designed to kill them,” says senior author Rosalie Sears, Ph.D., Krista L. Lake Chair in Cancer Research and co-director of the OHSU Brenden-Colson Center for Pancreatic Care.
Why DNA Repair Thwarts Cancer Treatment
To understand why this discovery is so critical, it’s important to understand how common cancer therapies work. Chemotherapy and radiation are designed to overwhelm cancer cells by causing massive, irreparable DNA damage. When a cell’s DNA is broken beyond repair, the cell typically dies.
However, if a tumor cell is highly efficient at repairing that damage, it can survive the treatment and continue to proliferate. Researchers at Oregon Health & Science University (OHSU) found that cells with the active, modified form of MYC repaired DNA more efficiently, making them significantly more likely to survive stressful conditions and DNA-damaging therapies.
The Impact on Pancreatic Cancer
This survival mechanism is especially dangerous in aggressive malignancies like pancreatic cancer. Using patient-derived pancreatic cancer cells and tumor data, the OHSU team found that cancers with high MYC activity also showed increased DNA repair activity. This correlation was linked to worse patient outcomes.
Gabriel Cohn, Ph.D., the study’s first author, notes that tumor cells in these aggressive cancers face extreme stress from poor blood supply and rapid growth. “Our work suggests that MYC helps these cells cope with that stress by actively promoting DNA repair,” Cohn explains.
Targeting the “Undruggable” Protein
For decades, MYC has been labeled “undruggable.” Its structure makes it incredibly difficult for drugs to bind to it without also damaging healthy cells. However, the discovery of MYC’s specific role in DNA repair offers a more precise target for drug development.
If scientists can interfere with MYC’s ability to repair DNA without shutting down its essential functions in healthy cells, they could make cancer cells far more vulnerable to existing treatments.
The OMO-103 Clinical Trial
OHSU is already moving toward clinical application. Researchers are currently investigating a first-in-class MYC inhibitor called OMO-103 through a “window of opportunity” trial. In this study, patients with advanced pancreatic cancer undergo biopsies both before and after receiving the drug to determine how blocking MYC alters the behavior of tumors in real-time.
Frequently Asked Questions
What is the MYC protein?
MYC is an oncogene that acts as a transcription factor, meaning it switches on genes that control cell growth and metabolism. It is abnormally active in the majority of human cancers.
How does MYC contribute to chemotherapy resistance?
Chemotherapy works by damaging the DNA of cancer cells. MYC helps these cells survive by physically moving to the sites of DNA damage and recruiting the proteins needed to fix the breaks, allowing the tumor to recover and continue growing.
Can MYC be blocked with medication?
While MYC was long considered “undruggable,” new research into its role in DNA repair is opening doors. A drug called OMO-103 is currently being tested in trials to see if blocking MYC can make pancreatic cancer more responsive to treatment.
By uncovering how MYC protects tumors from the inside out, researchers are moving closer to breaking the resistance of some of the most aggressive cancers, potentially transforming the prognosis for patients facing limited treatment options.