A new review highlights the growing importance of circular RNAs (circRNAs) in addressing one of the most pressing challenges in modern oncology: treatment-related toxicity. As advances in cancer therapies continue to improve survival rates worldwide, adverse effects linked to chemotherapy, radiotherapy, and immunotherapy remain a critical barrier to long-term patient outcomes and quality of life.
CircRNAs, a unique class of stable, closed-loop RNA molecules, are emerging as powerful regulators of cellular processes. Their ability to influence mechanisms such as oxidative stress, apoptosis, mitochondrial dysfunction, and DNA damage positions them at the center of toxicity pathways triggered by cancer treatments. These molecules are increasingly recognized for their dual role in both driving and mitigating harmful side effects across multiple organ systems.
The review underscores how circRNAs interact with key biological pathways to shape outcomes in cardiotoxicity, nephrotoxicity, neurotoxicity, and gastrointestinal injury. For example, certain circRNAs can amplify cellular damage by promoting inflammation and oxidative imbalance, while others provide protective effects by stabilizing cellular homeostasis and reducing tissue injury. This complex regulatory network highlights circRNAs as both risk indicators and protective agents in cancer care.
Beyond their mechanistic roles, circRNAs show strong potential as biomarkers for early detection of toxicity. Their high stability and tissue-specific expression make them promising tools for monitoring patient responses and identifying complications before they become clinically severe. In parallel, emerging strategies aim to harness circRNAs as therapeutic targets, offering new avenues to minimize adverse effects without compromising treatment efficacy.
The findings also point to the relevance of circRNAs in immune-related adverse events, particularly in the context of modern immunotherapies. By influencing immune signaling pathways and inflammatory responses, circRNAs may help explain variations in patient tolerance and open the door to more personalized treatment approaches.
Despite these promising developments, challenges remain in translating circRNA insights into clinical practice. Issues related to detection sensitivity, standardization, and functional validation must be addressed to fully realize their potential. Nevertheless, the expanding understanding of circRNA biology signals a transformative step toward safer and more effective cancer treatment.
This emerging field offers a compelling vision for the future, where targeting circRNAs could significantly reduce toxicity, enhance patient outcomes, and redefine the balance between treatment efficacy and quality of life.
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Reference
Jiawen Xian, Javeria Qadir, Burton B. Yang, Ting Ye, Role of circular RNAs in regulating toxicity induced by cancer therapies, Genes & Diseases, Volume 13, Issue 4, 2026, 101982, https://doi.org/10.1016/j.gendis.2025.101982

Funding
National Natural Science Youth Fund, China 82003138
Cooperative Scientific Research Project of the "Chunhui Plan" of the Ministry of Education, China HZKY20220575
Haiju plan High-End Talent Introduction Program of the Sichuan Provincial Department of Science and Technology (China) 2025HJRC0036
Medical Science and Technology Development Project of Clinical Medicine at Southwest Medical University (China) 2024LCYXZX24