“The data suggest that PRDX1 can predict responses to chemotherapy, and targeting PRDX1 could be a viable strategy to improve the efficacy of platinum chemotherapy.”
BUFFALO, NY – June 3, 2025 – A new research paper was published in Volume 16 of Oncotarget on May 19, 2025, titled “PRDX1 protects ATM from arsenite-induced proteotoxicity and maintains its stability during DNA damage signaling.”
In this study, led by first author Reem Ali and corresponding author Dindial Ramotar from Hamad Bin Khalifa University in Qatar, researchers discovered that a protein called PRDX1 helps maintain the stability of ATM, a key protein involved in repairing damaged DNA, especially when cells are under stress from arsenite exposure. The study found that without PRDX1, cells lose their ability to repair DNA and become more sensitive to chemotherapy. This finding suggests that targeting PRDX1 could improve the success of some cancer treatments.
PRDX1 is already known for its role in protecting cells from oxidative damage, but this study shows it also plays a role in the DNA repair process. ATM is an essential protein that detects breaks in DNA and starts the repair process. When PRDX1 is missing, ATM is rapidly lost, especially when cells are exposed to arsenite, a toxic substance found in the environment. Without ATM, the DNA repair system fails, leaving cells more vulnerable to damage.
By using both human cell lines and clinical samples from ovarian cancer patients, the team showed that high levels of PRDX1, along with ATM and MRE11 (another DNA repair protein), were linked to tumors’ aggressive features and lower patient survival rates. This pattern suggests that tumors with high PRDX1 may resist chemotherapy by increasing their DNA repair capacity. On the other hand, removing PRDX1 weakened the repair system and made cancer cells more responsive to DNA-damaging platinum drugs.
The study also showed that combining low doses of arsenite with drugs that either block ATM or damage DNA caused a much higher rate of cancer cell death in cells that lacked PRDX1. These results suggest a new treatment approach: lowering PRDX1 levels to make cancer cells more sensitive to DNA-damaging platinum therapies already in use. This highlights PRDX1 not only as a protector of cell function but also as a potential weak point in cancer cells.
“As such, we propose that small molecule inhibitors of PRDX1, or single nucleotide polymorphisms that compromise PRDX1 function, in combination with low doses of arsenite can be exploited to treat chemo-resistant tumours.”
These findings open the door for the use of PRDX1 as a biomarker to predict treatment response and as a promising target for new combination therapies. For patients with ovarian cancer and potentially other tumors, adjusting PRDX1 levels may help overcome drug resistance and improve outcomes.
Continue reading: DOI: https://doi.org/10.18632/oncotarget.28720
Correspondence to: Dindial Ramotar – dramotar@hbku.edu.qa
Keywords: cancer, redox signaling, homologous recombination, protein interaction, cell cycle, protein modification
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