# State‐of‐the‐Art Strategies for Circular RNA in Cancers: Opportunity and Challenge

## TL;DR

Circular RNAs are emerging as key regulators in cancer, offering new diagnostic and therapeutic opportunities despite challenges in their study and application.

## Contribution

This review provides a comprehensive overview of circRNA functions, biogenesis, and therapeutic potential in cancer, emphasizing recent advances and future directions.

## Key findings

- CircRNAs act beyond microRNA sponges, functioning as protein scaffolds and peptide templates in cancer.
- They play roles in tumorigenesis, immune evasion, and tumor–microbiome interactions, making them promising biomarkers.
- Emerging AI tools and engineered therapies like CAR-T are being explored to harness circRNA potential in precision oncology.

## Abstract

Circular RNAs (circRNAs) are characterized by their covalently closed structure, remarkable stability, and precise spatiotemporal regulation, evolving from once‐overlooked transcriptional byproducts to pivotal molecular regulators. In addition to their well‐established function as microRNA sponges, circRNAs serve as protein scaffolds, transcriptional modulators, and even templates for functional peptide synthesis. This review synthesizes recent breakthroughs across the entire circRNA life cycle, encompassing biogenesis, degradation, nucleocytoplasmic transport, and extracellular vesicle‐mediated secretion, while systematically analyzing their multifaceted involvement in tumorigenesis, immune evasion, metastatic dissemination, programmed cell death, and tumor–microbiome crosstalk. We highlight their exceptional potential as liquid biopsy biomarkers and critically assess translational applications in circRNA‐based vaccines, targeted delivery platforms, and engineered cell therapies like CAR‐T. Emerging artificial intelligence approaches that accelerate circRNA discovery, functional characterization, and therapeutic design are also discussed. Addressing current challenges in standardization and delivery methodologies, we propose future directions for incorporating circRNAs and their encoded proteins into precision oncology and next‐generation immunotherapies. Together, these advances position circRNAs as a transformative paradigm with the potential to revolutionize cancer diagnostics, targeted therapeutics, and RNA vaccine development.

Overview of circular RNA in tumors.