The role of mitochondria as therapeutic targets in the treatment of pancreatic ductal adenocarcinoma: opportunities and challenges

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is currently the fourth leading cause of cancer-related deaths worldwide. This is due to its complex microenvironment and high resistance to treatment. One of the key factors contributing to this resistance is the altered function of mitochondria in tumor cells, including high levels of oxidative phosphorylation (OXPHOS), a predominance of mitochondrial fusion processes, and increased autophagy, all of which are closely linked to cancer cell metabolism. The literature suggests three main therapeutic approaches: OXPHOS inhibition, modulation of mitochondrial dynamics, and autophagy suppression. Studies indicate that both reducing OXPHOS activity and inhibiting autophagy sensitize tumors to chemotherapy. Moreover, modulating mitochondrial dynamics effectively suppresses further tumor growth. Despite promising research on targeting mitochondria as a therapeutic strategy for PDAC, further studies are needed to determine the efficacy and safety of these approaches in humans.