Therapeutic potential of natural triterpenoids in pancreatic cancer

Pancreatic cancer remains one of the most lethal of malignancies with a 5-year survival rate of approximately 10% in the USA, largely owing to its late diagnosis, intrinsic chemoresistance, and high incidence of metastatic disease. Although gemcitabine-based chemotherapy is the standard treatment for advanced pancreatic cancer, inherent tumor heterogeneity and highly desmoplastic and immunosuppressive tumor microenvironment result in conventional cancer treatments having little impact on patient's disease course. Therefore, the development of novel and effective therapies is urgently required. Triterpenoids are naturally occurring secondary metabolites biosynthesized following the isoprene rule of Ruzicka, with a basic nucleus of 30 carbon atoms. Growing evidence from preclinical studies indicates natural triterpenoids as potential anticancer agents against pancreatic cancer. In this review, we synthesize research findings from available preclinical studies that investigated the therapeutic potential of natural triterpenoids on pancreatic cancer, particularly focusing on anticancer mechanisms involving activation of apoptosis, induction of autophagy, regulation of immune responses, inhibition of metastasis, and enhancement of chemosensitivity. We also discuss the key challenges and envisage future research directions in this rapidly evolving field. We conclude that natural triterpenoids are a valuable resource for developing novel therapeutic agents against pancreatic cancer. We also hope that the knowledge gained from this narrative review will be helpful in accelerating the translation of triterpenoid-based therapeutics into clinical practice.