Pancreatic cancer is a lethal malignancy with unsatisfactory response to standard chemotherapy and targeted agents. The molecular mechanisms that drive PDAC progression and resistance to therapy are complex and involve cross-talk between tumor cells and microenvironment components including stromal cells, soluble factors, epithelial-mesenchymal transition (EMT), immunoescape, and drug delivery [31].
One of the most promising strategies to target these processes is to use a combination of pharmacological agents that can affect multiple pathways simultaneously and synergistically. Fenbendazole is a common antiparasitic drug that also has been found to have antitumor properties in mice and human pancreatic cancer cells. It acts by interfering with the formation of microtubules, a protein scaffolding that gives cells their shape and structure. Textbook depictions of cells show cellular components floating in amorphous bags of liquid, but cells establish their shape and structure through a highly dynamic cytoskeleton made of microtubules. Microtubules are assembled and disassembled as the cell requires, with the assistance of a protein called tubulin.
We found that parbendazole markedly alters the distribution of microtubules in AsPC-1 and Capan-2 cells, interfering with their assembly and causing the formation of aberrant mitotic spindles. This phenotype correlates with a pronounced apoptosis induced by the drug, as shown by flow cytometry and PARP cleavage assays. In addition, we observed that the cytotoxic activity of parbendazole is significantly enhanced by its interaction with gemcitabine. These findings suggest that a combination of benzimidazole-based agents can effectively treat pancreatic cancer. fenbendazole for pancreatic cancer