Targeting macrophage-directed pathological processes in pancreatic ductal adenocarcinoma: Mechanisms and targeted...

Macrophages support the malignant transformation of pancreatic ductal adenocarcinoma cells by secreting cytokines and enzymes, which enhance tumor invasiveness and metastatic potential. In addition to promoting tumor growth, macrophages contribute to drug resistance, radioresistance, and immune evasion mechanisms by interacting with both cancer cells and other immune components. Their role in promoting angiogenesis further illustrates their importance in sustaining a tumor-supportive environment. These insights have led to growing interest in macrophage-targeted therapies. Approaches under investigation include reprogramming macrophages to adopt tumor-inhibiting functions, combining conventional chemotherapy or radiotherapy with macrophage-specific treatments to overcome resistance, using immunotherapies to modulate macrophage activity and enhance anti-tumor immune responses, and employing nanoparticle-based drug delivery systems for precise targeting. A deeper understanding of the specific mechanisms by which macrophages influence pancreatic ductal adenocarcinoma progression is essential. Such knowledge will pave the way for more effective treatments and offer new therapeutic options for patients with this aggressive disease.