RNA editing: an emerging frontier in cancer therapy - explorations, opportunities, and challenges

RNA editing is a critical regulatory mechanism that acts after transcription. Two types of RNA editing are A-to-I editing and C-to-U editing. The first one uses adenosine deaminase acting on RNA, while the second uses APOBEC complexes. RNA editing has an important role in cancer development in controls tumorigenesis and tumor progression through multiple mechanism. It allows for precise edits to RNA sites linked to cancer at a molecular level. At the microenvironmental level, it regulates the immune response by remodeling the immune landscape. RNA editing has dual roles in tumor progression and anti-tumor effects. The ability of some non-coding RNAs to perform the reverse function is shown to be useful in various important biological processes. The important processes include drug resistance, agitation, tumor suppressor gene expression, tumor microenvironment, metabolic regulation, and cancer cell migration. Both the over and under editing of RNA can cause tumors. Therefore, initiating and stopping editing needs to be strictly controlled for clinical purposes. Studies indicate RNA editing has a unique therapeutic potential by downregulating oncogenes, restoring mutated genes, and enhancing the efficacies of immunotherapy. Problems remain; however, with regard to targeting precision, safety, functional characterization, and the regulation of editing efficiency and extent. The ongoing evolution of specificity and tools may ensure that RNA editing emerges as a vital strategy in cancer therapeutics. Nevertheless, progress is hindered by enduring hurdles, such as off-target effects and variable editing efficiency, and has yet to be validated in larger and multi-site clinical trials. In the same vein, RNA editing may serve as useful references for surgical decisions. For example, RNA editing can be used to identify surgery risk, recurrence risk, and surgical approach selection due to its exact targeting capacity. It also helps intraoperative resection margins and adjuvant therapy to properly maintain the outcome postoperatively in the long term. Hence, surgical oncology researchers must explore RNA editing in-depth. It is worth noting that limited antitumor activity was observed in solid tumors in preclinical studies due to insufficient delivery of editing tools, indicating realistic translation expectation is needed.