Cytokines at the Crossroads of Mitochondrial Dysfunction and Inflammation in Colorectal Cancer: Implications for...

Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide, with surgery representing the cornerstone of curative treatment. Although surgical techniques and perioperative care have improved markedly, postoperative complications (POCs) still significantly affect early morbidity, prolong recovery and negatively influence long-term outcomes. These challenges have led to growing efforts to identify biological markers that could help predict adverse events and improve risk stratification. Inflammatory activation and mitochondrial dysfunction have emerged as interconnected contributors to postoperative vulnerability, and their measurable mediators represent attractive candidates for biomarker development. Cytokines, as central regulators of immune signalling, together with mitochondrial-derived danger signals (mtDAMPs) released during surgical trauma and ischemia-reperfusion injury, may enable earlier identification of patients at risk of POCs. In this review, we summarize current evidence linking key cytokines, including interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-1β and IL-10, to postoperative outcomes after CRC surgery and discuss mechanistic pathways through which cytokine signalling can modulate mitochondrial function, reactive oxygen species production and tissue integrity. We also highlight the translational potential of mitochondrial biomarkers such as circulating mitochondrial DNA, while acknowledging that CRC-specific clinical evidence remains limited and methodologically heterogeneous. Taken together, a deeper understanding of these interconnections, supported by standardized longitudinal perioperative profiling, could ultimately improve complication prediction and support more personalized strategies for POCs prevention, early detection and optimized recovery following CRC surgery.