Drugs and natural bioactive products in modulation of inflammatory pathways in cancer: preclinical and clinical evidence of inflammasomes, cytokine networks, and macrophage polarization

Abstract

Cancer remains a formidable global health challenge, with mortality projected to reach 16.3 million annually by 2040. Despite diagnostic and therapeutic advances, the escalating cancer burden necessitates innovative treatment strategies. Emerging evidence from molecular oncology and immunology has established chronic inflammation as a critical driver of cancer initiation, progression, and therapeutic resistance. While inflammation is an evolutionarily conserved defense mechanism essential for pathogen clearance and tissue repair, dysregulated inflammatory processes paradoxically promote tumorigenesis through immune suppression, tumor microenvironment remodeling, and proliferative signaling to malignant cells. First recognized in the 19th century through observations of leukocytic tumor infiltration, tumor-associated inflammation is now an established hallmark of cancer. Contemporary research demonstrates that inflammatory networks suppress antitumor immune surveillance while facilitating cancer cell survival, invasion, and metastatic dissemination. Given inflammation's central role in oncogenesis, its pharmacological modulation represents a promising therapeutic frontier for cancer prevention and treatment. This review examines anti-inflammatory pharmacotherapy in cancer management, emphasizing both synthetic drugs and natural products that modulate inflammasome activation, cytokine signaling, and macrophage polarization. We critically evaluate the molecular mechanisms underlying the antineoplastic effects of anti-inflammatory compounds and explore their translational potential as adjuvant or standalone therapies. By integrating mechanistic insights with clinical evidence, this review delineates approaches for targeting chronic inflammation to decelerate cancer progression, enhance treatment efficacy, and improve patient outcomes.