At Oregon Health & Science University in Portland, scientists have uncovered a hidden survival mechanism that explains why some of the deadliest cancers resist the very treatments designed to destroy them. Researchers discovered that the MYC protein—already known for fueling tumor growth—performs an unexpected second job: it actively repairs DNA damage caused by chemotherapy, allowing cancer cells to bounce back from treatments that should kill them.
The finding, published in Genes & Development, reveals a previously misunderstood facet of one of cancer's most notorious proteins. For decades, scientists have known that MYC goes haywire in most human cancers, but Rosalie Sears, Ph.D., and her team at OHSU's Brenden-Colson Center for Pancreatic Care, discovered that when DNA breaks from chemotherapy or rapid tumor growth, a modified form of MYC physically travels to the damage site and recruits the proteins needed to repair it. This process allows tumor cells to survive conditions that would otherwise destroy them.
"MYC isn't just helping cancer cells grow—it's also helping them survive some of the very treatments designed to kill them," explained Sears, senior author of the research. Gabriel Cohn, Ph.D., the study's first author, found that cells containing this active form of MYC repaired DNA damage more efficiently and were more likely to survive stressful conditions, including exposure to chemotherapy.
The implications are particularly stark for pancreatic cancer, one of the deadliest malignancies. Using tumor data and pancreatic cancer cells derived from patients, researchers found that cancers with high MYC activity showed increased DNA repair activity and were associated with worse patient outcomes. In pancreatic tumors, which experience extreme stress from rapid growth, poor blood supply, and aggressive treatment, MYC appears to function as a cellular escape hatch. These tumors can withstand the DNA-damaging assault of chemotherapy and radiation precisely because they're repairing damage faster than the treatments can inflict it.
For cancer therapy, this creates a paradox. Many chemotherapy drugs and radiation treatments work by overwhelming tumor cells with DNA damage beyond their capacity to repair. But when a cancer cell is exceptionally skilled at fixing that damage—as MYC-driven cancers are—it survives treatment and continues growing. Understanding this mechanism opens a new door for intervention.
The real excitement lies ahead. MYC has long been considered "undruggable" because its structure makes it difficult for drugs to bind safely without harming healthy cells. But MYC's newly revealed role in DNA repair may provide a more precise target. Sears and her team believe that interfering specifically with MYC's repair function—while leaving its other roles intact in healthy cells—could make cancer cells far more vulnerable to treatment. "If we can interfere with MYC's role in DNA repair without shutting down everything MYC does in healthy cells, we may be able to make cancer cells more vulnerable to treatment," Sears said.
OHSU researchers are already testing this theory. A window-of-opportunity trial is underway in which patients with advanced pancreatic cancer receive a drug called OMO-103, a first-in-class MYC inhibitor. Biopsies taken before and after treatment will help researchers understand how blocking MYC changes real tumors in living patients. The study, supported by the National Cancer Institute, represents a pivotal moment: transforming MYC from an undruggable villain into a tractable target. If successful, this approach could reshape how doctors treat some of cancer's most aggressive forms.