Pancreatic cancer is often diagnosed at a late stage, and most patients are at high risk of death from the disease. Research is underway to improve diagnosis and treatment, but so far new therapies have not shown significant clinical benefit. One strategy under investigation is to activate the immune system by using drugs to target the proteins that cancer cells use to grow and spread. Medications that block the activity of these proteins can be effective in shrinking tumors and prolonging survival, but only if the drug is given for a long enough period of time to have an effect. The researchers in the MIT study examined whether fenbendazole, an anti-parasite medication, could inhibit the growth of pancreatic cancer cells. The team used the cell lines AsPC-1 and Capan-2, both of which have mutations in KRAS and p53. The cells were treated with fenbendazole, mebendazole, oxibendazole and parbendazole at different concentrations for 72 hours. Cell viability was assessed by the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay. The results showed that fenbendazole and mebendazole reduced the viability of the cancer cells, but not oxibendazole or parbendazole. The lipophilicity of the four benzimidazole-based anthelmintics (CLogP values were 4.182 for fenbendazole, 4.074 for mebendazole, 3.072 for oxibendazole and 3.795 for parbendazole) was not related to their ability to suppress pancreatic cancer cell viability. In a separate study, Riggins and his team found that mebendazole, which was developed to eradicate roundworm and hookworm by starving them of their food source, also worked against pancreatic cancer cells. The drug works by halting the formation of tubulin, which is both a micro-skeleton of the inner cell and a highway for transport. Cancer cells rely on tubulin to function, and when the drug stops it from being produced, the cancer cell collapses from within. Riggins believes fenbendazole may have the same effect. His team is currently exploring whether the drug can reactivate a gene inside cancer cells called p53, which functions as a tumor suppressor. The researchers hope to begin human trials soon. The work was funded by the National Institutes of Health’s Pancreatic Ductal Adenocarcinoma Specialized Program of Research Excellence (SPORE) grants. These programs are designed to quickly translate basic scientific discoveries into early-phase clinical studies of potential therapeutics that can be tested in humans. Other SPORE-supported research includes the development of biomarkers to identify individuals at high risk of developing pancreatic cancer and to enable more precise detection and diagnosis, as well as efforts to develop treatments that can reactivate the tumor-suppressing p53 gene in people with pancreatic cancer. Additional projects focus on the development of novel therapeutic strategies that can be combined with immunotherapy or other approaches to treat metastatic pancreatic cancer. Those strategies include CD40 agonist antibodies and drugs that interfere with the interaction between PD-1 and TIGIT. Both of these types of therapy are currently being tested in phase III clinical trials for pancreatic cancer. The research is part of an MIT-led consortium that seeks to bridge biological and preclinical/translational cancer research, with the goal of identifying new ways to treat pancreatic cancer at all stages of the disease. fenbendazole for pancreatic cancer
