Modulation of radiosensitivity by myoferlin pharmacological targeting in human pancreatic cancer cell lines

Pancreatic ductal adenocarcinoma (PDAC) is the seventh leading cause of cancer-related deaths worldwide. Radiotherapy alone or combined with chemotherapy is a therapeutic modality implemented in different circumstances (neoadjuvant, adjuvant, symptomatic). Myoferlin is a protein implicated in membrane fusion and in membrane receptors recycling. It allows vesicle trafficking in cells. In PDAC, myoferlin is overexpressed and reported to be required for an optimal cell growth. We used an innovative small compound (WJ460) to target myoferlin in PDAC cell lines and reported a significative synergy between WJ460 and irradiation for different combinations. Pharmacological manipulation of myoferlin improves radiosensitivity in vitro. We believe we revealed a pancreatic cell vulnerability that can be exploited in the treatment of PDAC.