Dual-Targeting Strategies for Chronic Inflammation

Chronic inflammation is central to the pathogenesis of autoimmune disorders, metabolic syndromes, and cancers. Current therapeutic strategies include nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and Janus kinase (JAK) inhibitors. However, these treatments can have broad downstream effects and may not adequately address parallel compensatory mechanisms that contribute to chronic inflammation. Dual-drug strategies offer the potential to improve therapeutic efficacy by simultaneously modulating complementary inflammatory pathways. However, their successful clinical translation requires careful evaluation of both safety and efficacy. Here, we discuss representative strategies spanning the translational spectrum, from mechanistic proof-of-concept studies to clinically evaluated and approved therapies, highlighting the opportunities and limitations of dual-drug approaches. We also examine emerging candidates with clinical potential and identify key challenges that must be addressed to facilitate their broader therapeutic application.