In many cancers, primary tumor cells are known to intravasate into the peripheral circulation as circulating tumor cells (CTCs) under flow. These CTCs can interact with the receptor-bearing endothelial cell wall and, through sialylated carbohydrate ligands similar to leukocytes mediating interactions with selectins on the endothelium, subsequently migrate into tissues and eventually form micrometastases. Micrometastases are difficult to detect, and metastasis through the bloodstream contributes to a poor prognosis in many cancers. More than 90% of cancer-related deaths result from metastases.
Cornell University researchers are developing therapy that kills cancer cells circulating in the bloodstream. These researchers conjugated nanoscale liposomes with a mixture of recombinant human E-selectin (ES) protein and tumor necrosis factor (TNF)‒related apoptosis-inducing ligand (TRAIL). Many CTCs and cancer cell lines are known to have glycosylated ligands that enable adhesive interaction with ES, and the TRAIL binds to death receptors on cancer cell surfaces to induce apoptosis. This unique approach has demonstrated efficacy in vitro with human blood samples and in murine blood circulation. This repurposing of leukocytes in circulating blood is more effective than directly targeting cancer cells with soluble protein or liposomes.
Contributed by William Yarnall, RPh, CCP
Medical Writer, Connexion Healthcare