MCC researchers uncover new clues about a gene linked to colorectal cancer

A team of researchers from the University of Minnesota and the University of Miami is shedding new light on a gene called XPO1 and its role in colorectal cancer. Their findings were recently published in Cancer Research.

Scientists at the University of Miami discovered that the XPO1 gene is often mutated in patients with endometrial and colorectal cancers. At the University of Minnesota, researchers focused on understanding why colorectal cancer cells with this mutation don’t respond well to a common chemotherapy drug called Top1 inhibitors, or Top1i, which is often used to treat the disease.

“Our preclinical findings, or early-stage research, suggests a new way to treat colorectal cancer, the third leading cause of cancer deaths in the U.S., and may also apply to endometrial cancer,” said Hai Dang Nguyen, PhD, a researcher with the Masonic Cancer Center, University of Minnesota, and assistant professor at the U of M Medical School. “By pinpointing how XPO1 mutations affect DNA repair, we’re opening doors to more targeted treatment options.”

The team found that colorectal cancer cells with the XPO1 mutation activate stronger DNA repair responses after being treated with Top1i, which may help them survive. But when the researchers added a drug called Selinexor, which blocks the XPO1 protein, the effect was reversed. This suggests that combining Selinexor with Top1i may be a new and more effective approach to treating XPO1-mutated cancers.

“This work gives us a reason to explore Selinexor as a way to boost the effects of chemotherapy in tumors with this mutation,” said Wannasiri Chiraphapphaiboon, PhD, a postdoctoral fellow in the Nguyen Lab.

The team also found that the XPO1 mutation causes certain DNA repair proteins to end up in the wrong parts of the cell. They plan to study how this misplacement affects the cancer’s ability to respond to treatment. Next steps include looking at whether the same patterns apply to endometrial cancer.

This research was supported by the Masonic Cancer Center, Edward P. Evans Foundation, American Society of Hematology, the National Institutes of Health, and the American Association for Cancer Research, with support from Merck.

A version of this story was first published by the University of Minnesota Medical School.