Fenbendazole Offers Hope For Pancreatic Cancer Patients

The pancreas is a flat organ deep inside the abdomen behind the stomach that produces enzymes and hormones to digest food and control blood sugar. It is the third most common cause of cancer and is one of the deadliest with just a 1 percent five-year survival rate. But new research suggests that a cheap and already-approved antiparasitic drug may boost other treatments for the disease.

The results of a small but encouraging clinical trial offer hope for patients with pancreatic cancer, which is often in the late stages by the time it’s diagnosed and has few treatment options. Patients who received the drug fenbendazole in combination with other cancer therapies had improved outcomes, according to research published Monday in the journal Nature Medicine.

Fenbendazole is an antiparasitic medication used to treat parasitic infections such as roundworm, hookworm and tapeworm. It has also been shown to slow down cancer cell growth in laboratory tests and in animal models. But this is the first study to show that combining it with other drugs can improve its effects in pancreatic cancer, says researcher Kirsten Bryant at the University of North Carolina at Chapel Hill.

Bryant and colleagues treated mice with an experimental immunotherapy called PD-1 inhibitors, which unleashe the body’s natural immune system to attack tumors. They also gave the mice a drug called CD40 agonist antibodies that stimulated the activity of T cells, which help the body fight off tumors. In the mice, the combination therapy slowed tumor growth and killed the cancer in half of the animals. But in the 25 percent that were given both a PD-1 inhibitor and a CD40 agonist, tumors were completely eradicated.

Researchers theorized that fenbendazole might make the immunotherapy more effective by getting cancer cells to depend on a single source of energy. So they tried it out in laboratory experiments with human pancreatic cancer cells and genetically engineered mice. They found that when the drug is given alone, it doesn’t do much. But when it’s combined with a PD-1 inhibitor and a TIGIT inhibitor, it dramatically enhances the ability of the compounds to kill the cancer.

The compound, which they call 4l, has the same basic structure as fenbendazole and mebendazole, two other benzimidazole drugs. But it has an alkyl side-chain that enhances its effect on cells. When it was tested in genetically engineered paraganglioma and pancreatic cancer cells, it dramatically reduced the cells’ viability at low micromolar concentrations. Combination treatment of the compound with gemcitabine, a standard chemotherapy drug that targets pancreatic cancer, also exhibited synergistic effects in these cells. The research was supported by the Virginia and D.K. Ludwig Fund for Cancer Research. The next step is to test the drug in people with pancreatic cancer and other diseases. The findings support a national randomized clinical trial being planned by researchers at the University of Pennsylvania and Siteman Cancer Center at Barnes-Jewish Hospital in Washington, DC. That trial will be part of the NCI’s Experimental Therapeutics Clinical Trials Network. fenbendazole for pancreatic cancer