Treatment of Inflammatory Bowel Disease with Drugs Targeting PANoptosis

Inflammatory Bowel Disease (IBD), which includes Ulcerative Colitis (UC) and Crohn's Disease (CD), is characterized by chronic inflammation and disruption of the intestinal barrier, which is a key pathophysiological mechanism. The efficacy of existing therapies is often inadequate, underscoring the imperative to identify new therapeutic targets. Recently, the concept of PANoptosis has emerged as a critical pathophysiological mechanism in IBD. PANoptosis describes a coordinated form of regulated cell death that incorporates key features of apoptosis, necrosis, and pyroptosis, and is activated through the Panoptosome complex or similar pathways. Targeting central regulators, such as RIPK1 (with agents such as Necrostatin-1), has been shown to protect the intestinal barrier in preclinical models. Furthermore, the combination strategy involving inhibitors of Panapoptotic death (to address the cause of cell death) and established biological agents (e.g., anti-TNF-α) represents the most advanced therapeutic perspective. This review describes the role of Panapoptotic death in the pathogenesis of IBD, current therapeutic strategies targeting Panoptosis, available clinical and preclinical data, molecular tools and pharmaceutical interventions, and future directions that will determine the clinical exploitation of these mechanisms. Finally, Panoptosis is examined not only as a single therapeutic target but also as a platform for the development of combination therapies that lead to more personalized and effective treatment in IBD.