New MAEA function in DNA repair offers a potential route to overcoming chemotherapy resistance
A University of Alberta research team has identified a surprising new role for a protein once thought to be linked primarily to red blood cell development. The protein, macrophage erythroblast attacher (MAEA), appears to help regulate DNA repair and cell replication. When MAEA is removed or inhibited, cancer cells become more vulnerable to standard chemotherapy drugs, a finding that could reshape how clinicians approach treatment for several cancers.
How MAEA changes our understanding of chemo resistance
Previously, MAEA was associated with developmental processes and facial abnormalities when mutated. The new study, published in Science Advances, shows that MAEA also participates directly in the cell’s ability to repair DNA, a critical factor in how cancer cells survive chemotherapy. By screening ~900 genes for their role in defending cells against chemotherapy, the researchers highlighted MAEA as a key player in the damage response pathway. This discovery opens the possibility that MAEA could function as a biomarker to predict chemotherapy response or as a target to enhance drug efficacy.
From discovery to a potential treatment strategy
Led by Ismail Ismail, associate professor in the Department of Oncology, the team demonstrated that inhibiting MAEA compromises DNA repair, rendering cancer cells more susceptible to drugs used for colorectal, small-cell lung, and ovarian cancers. The researchers are pursuing a two-pronged approach: first, to test whether MAEA inhibition can reverse drug resistance in tumors that have already become resistant, and second, to identify combination therapies that block compensatory pathways cancer cells activate when MAEA is impaired.
Building the case with advanced tools and collaborations
The project combined experimental biology with cutting-edge modelling. After pinpointing MAEA’s new role, the team partnered with biochemistry professor Mark Glover to apply AlphaFold modeling. This AI-based tool helped predict how MAEA mutations observed in children with developmental disabilities could affect the protein’s role in DNA repair. The collaboration extended to Université Laval to map compensatory pathways that cancer cells adopt when MAEA is not functioning, informing potential combination treatments that could block both routes to survival.
Independent replication by a research group at the University of Cambridge has corroborated the Alberta findings, adding confidence to the potential relevance of MAEA across different contexts and populations.
Clinical outlook: biomarkers, new therapies, and next steps
While developing MAEA-targeting drugs could take several years, the researchers see near-term potential in using MAEA as a biomarker. By identifying which patients are likely to respond to chemotherapy, clinicians could tailor treatments more effectively, sparing some patients from ineffective regimens and their toxic side effects. In the longer term, the team hopes to design drug strategies that inhibit MAEA or disrupt its interaction networks in cancer cells, particularly in tumors where MAEA is overexpressed.
Ismail notes that the approach might be adaptable beyond colorectal, ovarian, and lung cancers, and is already being tested in tissues from patients who have relapsed after standard therapy. The goal is to determine whether dual-blockade strategies—targeting MAEA and the cancer cell’s backup repair pathways—could improve relapse-free survival for more patients.
What this means for patients and developmental disorders
The study’s dual relevance is striking. For cancer patients, the work offers a potential way to resensitize tumors to chemotherapy or to predict who will benefit most from certain regimens. For children with developmental disorders, understanding MAEA’s function in DNA repair could illuminate how certain mutations contribute to disease, guiding future diagnostic or therapeutic research.
Bottom line
The MAEA discovery adds a new layer to our understanding of cellular repair mechanisms and drug resistance. Although translating this knowledge into routine clinical practice will take time, the research lays a solid foundation for biomarker development and potential combination therapies. The team’s ongoing work with international collaborators and patient-derived tissues will determine how best to move MAEA from the lab to the clinic, with the aim of improving outcomes for cancer patients and offering new insights into developmental disorders.
