Molecular pathways in cancer-related inflammation

Accumulating evidence shows that chronic inflammation is associated to increased risk of cancer. An inflammatory component is present also in the microenvironment of tumours epidemiologically unre-lated to inflammation. Extensive investigations over the past decade have uncovered many of the important mechanistic pathways underlying cancer-related inflammation. Pathways linking inflamma-tion and cancer have been identified: an intrinsic one (driven by genetic events that cause neoplasia) and an extrinsic one (driven by inflammatory conditions which predispose to cancer). Smouldering inflammation is a component of the tumour microenvironment and is a recognized hallmark of cancer. Key orchestrators at the intersection of the intrinsic and extrinsic pathways include transcription fac-tors (e.g. Nuclear Factor kappa-B, NFκB) that modulate the inflammatory response through soluble mediators (cytokines, chemokines) and cellular components (e.g. tumor-associated macrophages), promoting tumorigenesis. NFκB aids in the proliferation and survival of malignant cells, promotes an-giogenesis and metastasis, subverts adaptive immunity, and alters responses to hormones and che-motherapeutic agents. Emerging evidence also suggests that persistent inflammation promotes ge-netic instability. Thus, cancer-related inflammation represents a target for innovative diagnostic and therapeutic strategies