Beyond mutations: personalising oncology via RNA-editing

Adenosine-to-inosine (A-to-I) RNA-editing, catalysed by ADAR enzymes, is a dynamic layer of post-transcriptional regulation that significantly diversifies the cancer transcriptome and proteome. A-to-I editing, the most frequent and well-established form of editing in human cancer, holds greater immediate relevance for personalised oncology than the less mapped C-to-U “editome” landscape. By recoding oncogenes and tumour suppressors (e.g., AZIN1, NEIL1), modulating drug response, and generating immunogenic RNA-editing-derived neoantigens, A-to-I events directly influence tumour progression, heterogeneity, and immune recognition. These roles establish RNA-editing profiles as promising biomarkers for patient stratification and prognosis. Furthermore, the integration of editing data with multi-omics and machine learning is accelerating the development of personalised therapeutic strategies. These include ADAR-guided RNA correction, mRNA vaccines encoding edited neoantigens, and RNA interference, offering reversible and tailored intervention points. Despite challenges in delivery, specificity, and clinical translation, A-to-I RNA-editing represents both a fundamental cancer mechanism and a versatile toolkit, driving the next generation of precision oncology beyond the constraints of the genomic blueprint.