Ashutosh Kumar Maurya, Sheefa Mirza
Exosome-derived microRNAs (miRNAs) have recently been recognised as important players in the process of intercellular communication in CRC, thus allowing tumour cells to affect not only each other but also the whole milieu of interactions occurring in the tumour microenvironment and metastatic niches. The growing body of evidence points to selective packaging of exosomal miRNAs via controlled biogenesis mechanisms and modulation by oncogenic signalling and microenvironmental stress. After being delivered to target cells, these miRNAs affect interrelated signalling pathways involved in the epithelial-mesenchymal transition, stemness, immune escape, angiogenesis, metastasis niche development, and drug resistance. Instead of being regarded as simple biomolecular markers, exosomal miRNAs are better understood as regulators of networks of processes that allow tumour cell populations to coordinate their response to external stimuli and therapeutic interventions. This view can shed light on tumour heterogeneity, metastasis, and resistance to treatment in CRC. At the same time, their high biological stability in blood plasma has raised hopes for their clinical utility as markers of liquid biopsy and therapeutic targets. However, further progress in clinical translation is hampered by several obstacles, such as extracellular vesicle heterogeneity, methodological variability, and lack of standardisation. This review synthesises current knowledge on exosome biogenesis, selective miRNA sorting, tumour microenvironment communication, and therapy resistance in CRC. In addition, it highlights emerging systems biology, single-vesicle, and artificial intelligence-based approaches that may improve biomarker robustness and translational relevance. Collectively, this review argues that integrative and mechanism-driven strategies will be necessary to advance exosomal miRNAs from exploratory biomarkers toward clinically meaningful applications in precision oncology.