Acinar-to-Ductal Metaplasia: Bridging the Gap Between Cellular Plasticity and Treatment Innovations in Chronic Pancreatitis

Chronic pancreatitis (CP) progressively destroys and fibroses the pancreatic parenchyma, ultimately impairing exocrine and endocrine functions. Acinar-to-ductal metaplasia (ADM), the transformation of acinar cells into duct-like cells, plays a critical role in the progression of CP. This review first provides an overview of the plasticity of various cell types in the exocrine pancreas. It then delves into the mechanisms underlying ADM, focusing on its driving factors, including genetic mutations, environmental influences, and signaling pathways such as Notch. Finally, it discusses emerging therapeutic strategies, such as small molecule targeted drugs, nanomaterial-based drug delivery platforms, and cell regeneration therapies, that effectively alleviate inflammation and fibrosis. Although progress has been made, significant challenges remain in understanding the complex mechanisms of ADM and in ensuring the safety and efficacy of these therapies. This review aims to provide an in-depth understanding of the role of ADM in CP and to pave the way for efficacious therapeutic options.