By Alok Ranjan, Parul Gupta, and Sanjay K. Srivastava
Breast cancer is a devastating disease. It is responsible for the second highest number of cancer related deaths in the United States. According to the World Health Organization, breast cancer is the most common type of cancer in women all over the world and is claiming thousands of life each year. Breast cancer cells mainly migrate (metastasize) to lungs, liver, bone, and brain. Metastasis is responsible for 90% of human cancer deaths.
Although there are several treatment options available to treat breast cancer metastasis (such as surgery, chemotherapy, and radiation therapy), the outcome is very poor. Moreover, metastasis to the brain is a death sentence to patients because most drugs cannot reach brain due to the blood-brain barrier. The blood-brain barrier is a protective cover for the brain, which in most of the cases restricts chemotherapeutic agents from the brain. So there is an urgent need to search for agents that can cross the barrier and kill breast cancer cells lodged in the brain.
Our team evaluated many antipsychotic drugs in the laboratory for anticancer effects against breast cancer and identified penfluridol, which showed the best anticancer effect in our screening process. Penfluridol is known to treat psychotic disorders, especially schizophrenia, and can reach the brain by crossing the blood-brain barrier. It is a class of first-generation antipsychotics under the diphenylbutylpiperidine group.
To test penfluridol in the animal model of breast cancer metastasis to brain, we injected breast cancer cells in the left ventricle of the mouse heart, which, through circulation, lodged in the brain (one of the metastatic sites of breast cancer). We used this model because it mimics the actual patient scenario in which breast cancer cells metastasize to the brain. The cells we injected were tagged with a protein called luciferase, which emits light/luminescence after reacting with luciferin. We then imaged the live mice noninvasively after injecting luciferin using a Caliper IVIS imaging system. We were able to see the signals of breast cancer cells in the brain of mice within 15 minutes of intracardiac injection of breast cancer cells.
A group of mice with breast cancer cells in the brain were given penfluridol orally, while the other group remained untreated and served as the control. Our results showed that the tumor in the brains of the control mice grew rapidly. On the other hand, in the treated group, penfluridol suppressed the growth of breast cancer cells in the brain by 82%. To the best of our knowledge, our study for the first time demonstrated the antimetastatic effects of penfluridol in vivo in a novel breast tumor metastasis model. Most importantly, penfluridol is already in clinical use as an antipsychotic drug with an established safety record; therefore, any positive findings from our studies can be rapidly translated to the clinics for undertaking a clinical trial to treat advanced metastatic breast cancer patients.
Our team will present its research, abstract no. T2087, on May 20, 2014 from 10:00 am–2:00 pm PST in the Bayside Pavillion. Learn more using the NBC app for smartphones and devices.