New findings reveal MAEA’s unexpected function in DNA repair and cancer therapy
A University of Alberta research team has uncovered a surprising new role for the MAEA protein, historically associated with red blood cell development and linked to developmental disorders. In a study published in Science Advances, the researchers show that MAEA also helps control DNA repair and cell replication. When MAEA is removed or inhibited, cancer cells become more vulnerable to chemotherapy drugs, suggesting a potential strategy to overcome drug resistance in several cancers.
How the team identified MAEA’s role in chemoresistance
The scientists conducted a broad screen of nearly 900 genes to identify those involved in a cancer cell’s defense against chemotherapy commonly used for colorectal, small-cell lung, and ovarian cancers. Through this screen, MAEA emerged as a key player in the cell’s repair mechanisms. The team then investigated how MAEA’s function impacts treatment outcomes, linking gene activity to a cell’s ability to repair damage caused by chemotherapy.
Collaborative use of cutting-edge tools
To understand the consequences of MAEA dysfunction, the researchers collaborated with biochemist Mark Glover to apply AlphaFold modeling. This AI-based prediction tool helped them visualize how MAEA mutations found in some developmental disorders might affect its newly identified role in DNA repair. The modelling provided a clearer picture of how MAEA helps cells recover from chemotherapy-induced damage and how mutations could influence this process.
Mapping compensatory pathways in cancer cells
Understanding where MAEA fits in required identifying alternative pathways cancer cells may use when MAEA is not working properly. In collaboration with Université Laval, the team pinpointed compensatory mechanisms that cancer cells deploy. The idea is to develop combination treatments that simultaneously block MAEA-dependent repair and these backup pathways, thereby enhancing chemotherapy efficacy and reducing resistance.
Independent verification and broader implications
The University of Cambridge group has independently reproduced the U of A team’s findings, underscoring the robustness of MAEA’s newly described function. The discovery challenges the old view of MAEA as solely involved in blood cell development and related developmental disorders, expanding its relevance to cancer biology and treatment responsiveness.
From bench to bedside: potential clinical implications
Currently, MAEA could serve as a biomarker to identify patients who will respond best to certain chemotherapies. Elisa Zeinali, the study’s first author, notes that specific cancers produce higher levels of the MAEA protein, opening the door to targeted strategies that improve outcomes for patients undergoing chemotherapy. While developing drugs specifically targeting MAEA will take years, its value as a biomarker could be realized sooner, helping personalize treatment decisions and sparing patients from ineffective therapies.
Next steps and patient impact
The University of Alberta team is expanding their work with American cancer researchers to test the approach on tissue from patients who have relapsed and have limited options. They are also exploring whether MAEA-modulating strategies can enhance a broader range of chemotherapy drugs. This moves the research toward real-world clinical trials, with the potential to improve survival and quality of life for cancer patients while also informing treatment for certain developmental disorders linked to MAEA dysfunction.
Conclusion: a promising avenue in the fight against chemo resistance
MAEA’s newly discovered role in DNA repair adds a promising dimension to cancer therapy. By revealing how the protein contributes to drug resistance and how this resistance might be reversed or tempered, the work points toward smarter, more effective treatment strategies. As scientists continue to translate these findings into biomarkers and targeted approaches, patients could soon benefit from more precise chemotherapy that works with the body’s own repair systems rather than against them.
