Despite the recent success with targeted therapies, pancreatic cancer remains among the deadliest tumors in humans. Its resistance to standard chemotherapies and newer immunotherapy approaches is often due to mutations in the KRAS gene that promote tumor growth and metastasis. A team at MIT has developed a treatment strategy that doubled survival in mice with pancreatic cancer by targeting the KRAS mutations, and they are now working to boost the treatment’s effectiveness by pairing it with other drugs that activate a patient’s immune system to attack their tumor.
The researchers studied the effect of fenbendazole, which is used to treat helminth infections and is sold as the generic drug mebendazole, on pancreatic cancer cells. They found that even low concentrations of fenbendazole significantly affected cell growth and clonogenicity in AsPC-1 and Capan-2 pancreatic cancer cells. They also found that fenbendazole induced DNA damage in the cells, which may be a result of the drug’s anti-mitotic effect.
In the future, the authors hope to further investigate the underlying mechanism by which fenbendazole inhibits the growth of pancreatic cancer cells. They plan to combine fenbendazole with other drugs that are currently in development, including PD-1 inhibitors, TIGIT inhibitors and CD40 agonist antibodies. In addition, they are studying whether fenbendazole interacts with other genes that promote the development of pancreatic cancers, such as HER2, ERBB2 and NOTCH. Moreover, they will explore whether the fenbendazole-associated effects are modulated by other molecular targets that are involved in conferring chemoresistance or promoting epithelial-mesenchymal transition (EMT) and supporting immunoescape, such as EGFR, phosphoinositide 3-kinases/protein kinase alpha/mammalian target of rapamycin, cholecystokinin receptors and WNT/-catenin pathways. fenbendazole for pancreatic cancer