Advances in siRNA and synbiotic therapies for colorectal cancer: a molecular and microbiota perspective.

Colorectal cancer (CRC) remains a major global health challenge, with rising incidence and mortality despite advances in conventional therapies, often limited by recurrence, toxicity and drug resistance. siRNA-based therapeutics offer a precision approach by selectively silencing oncogenic and chemoresistance-related genes; but their clinical application is hindered by delivery, stability and off-target effects. Concurrently, synbiotics (prebiotics and probiotics) modulate gut microbiota, immune responses and inflammatory pathways involved in CRC progression. Integrating siRNA targeting with synbiotic-mediated microbiome modulation provides a complementary strategy addressing molecular and microenvironmental drivers of CRC. This review highlights key pathways, delivery strategies, co-therapeutic approaches and translational challenges, emphasizing the potential of combined RNAi and microbiome-based therapies for improved CRC management.