Non-Coding RNAs in Cancer Treatment Resistance: Mechanistic Insights with a Focus on Circular RNAs.

Despite progress in cancer therapies, resistance to treatment remains a significant hurdle, fuelingtumor recurrence and metastasis, and creating an urgent need for innovative strategies to enhance efficacy. Chemotherapy and radiotherapy are mainstays in cancer care, yet therapeutic resistance driven by complex and multifactorial mechanisms often limits their success. Circular RNAs (circRNAs) have recently emerged as crucial players in cancer biology, especially in the context of resistance across various cancers, including gastric, lung, breast, and hepatocellular carcinomas (HCC). These uniquely stable, circular molecules regulate cellular responses to treatment by influencing key processes such as DNA repair, signalling pathways, and survival mechanisms. Acting as molecular "sponges," circRNAs modulate other non-coding RNAs like miRNAs and lncRNAs, thereby affecting resistance-linked genes and pathways. Unraveling the circRNA-mediated mechanisms underlying resistance offers a new direction for combating drug resistance. By targeting these pathways, researchers are identifying novel therapeutic approaches that could improve patient outcomes, representing a transformative step toward precision medicine and reshaping future cancer treatments.