‘We have an obligation to help others’
Mays Cancer Center Annual Report
As Arhan Rao watched his grandfather become ill with cancer and die, a goal formed in the teenager’s mind. He would become an oncology physician and researcher and discover a new generation of cancer treatments. While still in high school, Rao learned the fundamentals of laboratory research during his summer internships at The University of Texas Health Science Center at San Antonio.
Now, clinical trials based on Rao’s lab observations about an existing drug are underway in breast and brain cancer at the Mays Cancer Center, one of only four National Cancer Institute-designated Cancer Centers in the state. Imipramine, a drug approved by the U.S. Food and Drug Administration to treat depression, is slowing tumor growth in the human breast cancer study at the center.
Rao is second author on a paper published in the peer-reviewed journal Cancer Letters. In mouse and human tumor cells, imipramine inhibited triple-negative and estrogen receptor-positive breast cancers that are notoriously difficult to treat in people.
“While researching initiatives from the National Cancer Institute, I found that the NCI has given priority to repurposing FDA-approved drugs as cancer treatments,” Rao said. “These drugs will be safe, as they are used to treat other diseases. If the same drugs work to kill cancer cells, then they can be used in clinics right away.”
Rao discussed the idea with his faculty mentor, Ratna Vadlamudi, PhD, professor of obstetrics and gynecology at the health science center and co-leader of the Cancer Development and Progression Program at the Mays Cancer Center. The Vadlamudi lab hosted Rao while he was a student attending high school in San Antonio’s Northside Independent School District.
“Dr. Vadlamudi mentioned that an FDA-approved drug library exists and that I could test those drugs in an unbiased way to find out if they work,” Rao said. “I began screening candidate drugs and discovered that imipramine was able to stop the growth of cancer cells.”
“When human patients receive chemotherapy and other treatments, they may develop depression,” Vadlamudi said. “Imipramine is one of the antidepressants prescribed for them, and the NCI library indicated that it might have anticancer activity. [Rao] was curious to delve into this.”
Rao’s explorations provided evidence that imipramine has potent anticancer activity. By reducing estrogen signaling, imipramine stunts the growth of estrogen receptor-positive breast cancers, he found. The drug also interferes with DNA repair, which curbs the ability of triplenegative breast cancers to proliferate, the lab discovered.
The breast cancer clinical trial is directed by Virginia Kaklamani, MD, leader of the Breast Oncology Program at the Mays Cancer Center and professor of medicine at the health science center. The team gave imipramine to women who had been newly diagnosed with breast cancer and awaited surgery.
“We typically have a window of two to three weeks or so between the diagnosis and the surgery triple and this is an opportunity for us to give patients a drug and test to see how it does on the cancer tissue,” Kaklamani said.
The care team obtains a biopsy as part of the initial diagnosis and another tissue specimen during surgery.
“This affords two time points so we can see how the cancer has changed with the imipramine treatment without having to subject women to more biopsies,” Kaklamani said. “We did that in 15 patients, and overall, we were able to show that imipramine can decrease the tumor growth.”
This small pilot study, funded by the Mays Cancer Center, is a preliminary experiment to show that imipramine is an active drug in breast cancer, Kaklamani said.
Rao, who spent summer and holiday breaks at the lab, intends to pursue a career in medicine and improve the lives of patients.
“I believe, as a society, we have a moral obligation to help others,” Rao said. “Many cancer patients relapse after a couple of years, and that is so incredibly sad. We need to decrease that. We need to help researchers and society in general develop additional safe and effective treatment options. This project with imipramine is a part of that.”
