Schizophrenia Drug Halts Pancreatic Cancer Growth

Drugs used to treat schizophrenia can slow tumor growth and metastatic spread in mice with pancreatic cancer, a study published in Gastroenterology found.

Pancreatic cancer is extremely aggressive and starts spreading to other parts of the body early on. The disease generally has a poor prognosis and often times, will remain asymptomatic for a long period of time causing the disease to be diagnosed when it is in its later stages.

“While the overall 5-year survival rate of all cancer patients stands at 63%, it is only about 5% for pancreatic cancer — a number that has remained largely unchanged for the last 3 decades,” said corresponding study author Yasser Riazalhosseini.

In addition, this type of cancer rapidly develops a resistance to chemotherapy drugs. For the study, researchers undertook a large-scale analysis of gene activities in 195 pancreatic cancer cases.

“We leveraged quantitative and computational biology approaches that we have established in order to identify genes that may play a central role in several pancreatic cancer-relevant signaling pathways,” Riazalhosseini said. “We found that the gene for the dopamine receptor DRD2 was significantly more active in cancer cells than in healthy pancreatic cells. And the levels of DRD2 protein found in the cancer cells were 4 times normal levels.”

By blocking the dopamine receptor, it inhibits cancer growth. But how this receptor protein, which is known for its role in schizophrenia and psychotic disorders, influences the malignant characteristics of cancer cells was something researchers wanted to find out.

Using pancreatic cancer cell lines, researchers turned off the DRD2 gene, and found these cells grew at a much slower pace, and formed smaller tumors when transferred to mice. DRD2 is a key molecule in schizophrenia that is targeted by multiple psychopharmaceutical agents.

Two oft-prescribed antipsychotic medications for the treatment of schizophrenia are pimozide and haloperidol. When researchers used these substances, they were able to substantially inhibit the growth and impede the mobility of pancreatic cancer cell lines successfully.

Researchers then transferred the human pancreatic cancer cells to mice, and allowed the cells to grow into tumors. The mice were treated with haloperidol, which resulted in the development of smaller tumors and fewer metastases than in untreated mice.

“The fact that we show established medications that inhibit DRD2 have promising results for treating pancreatic cancer paves the way for a faster translation of our findings into the clinic through a drug repositioning strategy,” Riazalhosseini said. “At the initial step of this strategy, we are examining the efficacy of different doses of DRD2 inhibitors in different animal models before moving on to patients.”