Inflammation and carcinogenesis: molecular targets and small-molecule intervention strategies

Inflammation is a finely tuned host defense mechanism whose perpetual activation is a driver, promoter, and supporter of carcinogenesis. Key mediators of chronic inflammatory processes, viz. NF-kB, JAK-STAT, inflammasomes, reactive oxygen species (ROS), and cytokine network, if left unanswered, foster the tumour-supportive environment. Within the tumour microenvironment (TME), inflammatory cells, in combination with stromal and cancerous cells, modulate these pathways and regulate critical tumour hallmarks. Therefore, efforts have been made to understand and tackle the interface between the inflammation-cancer axis, but therapeutic outcomes remain limited. In this context, integrating systems-level biological insights with precision-driven medicinal chemistry may pave the way towards next-generation anti-inflammatory chemotherapeutics. The current review underlines the critical involvement of inflammation in cancer development by providing a comprehensive overview of key molecular pathways. A special emphasis was placed on understanding the medicinal chemistry campaign over the last 5 years for the development of inflammation-targeting small-molecule therapeutics in cancer.