Science Advances reports that a team from the University of Alberta has identified a previously unknown function for the protein MAEA, which was formerly linked only to developmental disorders. Their discovery could transform how patients respond to cancer treatment.
In their study, the researchers show that MAEA regulates DNA repair and cell replication. The removal or inhibition of this protein makes tumor cells far more susceptible to chemotherapy agents.
“Because of MAEA’s novel role in DNA repair, our preliminary data suggest that we can reverse drug resistance,” explains Principal Investigator Ismail Ismail, an associate professor in the Department of Oncology. “This insight could broaden treatment options for both developmental conditions and cancer.”
The team examined MAEA’s function using chemotherapeutics commonly employed against colorectal, small‑cell lung, and ovarian cancers. By screening almost 900 genes, they identified the genes that help cells withstand these drugs.
After honing in on MAEA’s importance in repair and replication, the group worked with biochemist Mark Glover to employ AlphaFold, an AI‑driven modeling tool, to evaluate how mutations found in children with developmental disabilities affect the protein’s new activity.
They also collaborated with research staff at Université Laval to map the compensatory pathway that cancer cells activate when MAEA is impaired, with the goal of simultaneously blocking both pathways.
Presently, the Alberta investigators are partnering with an American cancer consortium to test this strategy on tissue from patients whose disease has recurred and who have exhausted all other options. They are also extending the work to other classes of chemotherapeutic drugs.
A separate laboratory at the University of Cambridge has independently replicated the findings.
Prior to this work, MAEA was thought to function only in red blood cell development, and its malfunction had been associated with neurodevelopmental delays and facial dysmorphisms.
First author Elham Zeinali, a Ph.D. student, notes that the new data provide a deeper understanding of how genetic mutations influence child development.
She adds, “Certain cancers overexpress the MAEA protein, so targeting it with drugs may improve outcomes for patients undergoing chemotherapy.”
Although drug design targeting MAEA is a long‑term goal, Ismail sees potential to use MAEA as a biomarker in the near future to identify patients most likely to benefit from chemotherapeutic regimens.