Receptor-Guided Therapeutic Targeting of the Inflammation-Cancer Axis: Molecular Mechanisms and Emerging Drug Discovery Strategies

Chronic inflammation is a key driver of carcinogenesis, promoting tumour initiation, progression, metastasis and therapeutic resistance through receptor-mediated signalling networks. Chemokine receptors, Toll-like receptors (TLRs), G-protein-coupled receptors (GPCRs), nuclear receptors, and receptor tyrosine kinases (RTKs) integrate inflammatory cues with oncogenic pathways, including NF-κB, STAT3, PI3K/ Protein Kinase B (AKT) and MAPK, to sustain tumour-promoting inflammation within the tumour microenvironment. This review summarizes the molecular mechanisms linking chronic inflammation and cancer, highlighting receptor cross-talk and the roles of major inflammatory mediators such as IL-6 and TNF-α. We discuss emerging receptor-guided drug discovery strategies, including structure-based design, CRISPR-enabled target identification, allosteric and biased ligands, PROTAC-mediated degradation and multi-omics and AI-assisted target prioritization. Finally, we examine translational challenges, biomarker-guided precision medicine and future opportunities for developing personalized receptor-targeted therapies that disrupt the inflammation-cancer axis and improve clinical outcomes.