The interplay between chronic inflammation and tumorigenesis: unraveling the inflammation-driven axis

Chronic inflammation is now recognized as an important factor linking tissue damage to the development of cancer. Epidemiological studies have suggested that 20%-25% of cancers are related to chronic inflammation, as exemplified by chronic hepatitis B infection inducing hepatocellular carcinoma (HCC) or Helicobacter pylori infection inducing the development of gastric cancer. In chronic inflammation, an overexpression of signaling pathways such as NF-κB, JAK/STAT3, MAPK and NLRP3 at the molecular level leads to continuous upregulation of the secretion of pro-inflammatory cytokines and immune-metabolic reprogramming. These processes result in DNA damage, genetic mutations and epigenetic changes, promoting the initiation and progression of tumors. Interactions between pro-inflammatory cytokines and different types of cellular constituents reshape the tumor microenvironment (TME), leading to fibrosis, chaotic angiogenesis, and immune suppression-favoring further immune escape by tumors and perpetuating cancer stemness. Furthermore, through epigenetic as well as other molecular mechanisms, chronic inflammation fosters tumor drug resistance. So far, anti-inflammatory agents (e.g. anti-inflammatory drugs and natural bioactive compounds) as well as forms of dietary intervention have been associated with a reduced risk of cancer development in selected inflammation-associated settings, emphasizing that inflammation control may contribute to cancer prevention when supported by appropriate patient selection and clinical validation. In addition, new anti-inflammatory drug interventions targeting the IL-6/STAT3, NF-κB and NLRP3 pathways have shown good prospects for inhibiting tumors while modulating the immune microenvironment. Inflammatory biomarkers and epigenetic inflammation scores may support cancer risk stratification, early detection, prognostic assessment and treatment monitoring; however, most should be interpreted as complementary laboratory tools rather than stand-alone diagnostic tests, and their clinical implementation requires standardized analytical platforms, harmonized cutoff values, demonstration of incremental utility and prospective validation.