Reciprocal control of genome instability and RNA processing in cancer: Mechanisms and therapeutic opportunities.

Genomic instability and dysregulated RNA processing are mechanistically intertwined in cancer, forming a bidirectional genome instability–RNA processing circuit linked to resistance, immune modulation, and vulnerabilities beyond DNA-only biomarkers.

• Why it matters: DNA-centric biomarkers miss clinically relevant phenotypes because they do not capture how RNA processing and genome instability reinforce each other through shared regulatory mechanisms.
• What they did: The work synthesizes evidence that chromosomal instability, mismatch-repair deficiency, and homologous recombination deficiency reshape RNA splicing, 3' end formation, and RNA surveillance, while aberrant splicing, polyadenylation, and RNA modifications feed back to impair DNA repair and increase replication stress.
• The result: The unified framework supports integrated DNA–RNA biomarker strategies and rational combination approaches for diagnosis, treatment stratification, and therapeutic exploitation in cancer.

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