Beyond the ceiling: A critical analysis of microRNA research in cutaneous T-cell lymphoma and a roadmap forward

MicroRNAs (miRNAs) have been studied in cutaneous T-cell lymphoma (CTCL) for more than 15 years, revealing oncogenic and tumor-suppressive networks, the JAK/STAT-miRNA signaling circuit, diagnostic classifiers, and therapeutic miRNA targeting (Cobomarsen, targeting miRNA-155). Yet, no miRNA diagnostic has reached clinical practice. We synthesize the CTCL miRNA literature and argue that translation has stalled as a result of 2 interrelated limitations-methodological and biological-including reliance on bulk-tissue profiling and the intrinsic miRNA biology, including modest regulation of multiple pathways. Future strategies encompassing single-cell and subclone profiling, targeted anti-miRNA delivery, multiomics integration, miRNA network remodeling, multicenter validation, and artificial intelligence-driven bioinformatics may herald a golden renaissance for miRNAs.