Anti-Depressant Drug Offers Hope to Treat, Prevent Breast Cancer
Mays Cancer Center Annual Report
A discovery in a research lab at the Mays Cancer Center has led to a clinical trial repurposing imipramine, a drug originally designed to treat depression, to determine if the drug not only treats but also prevents breast cancer.
In his lab, Manjeet Rao, PhD, interim director of the Greehey Children’s Cancer Research Institute, studied an FDA-approved anti-depressant called imipramine to determine if it could block breast cancer growth by preventing breast cancer cells from repairing themselves.
Dr. Rao has been studying the unique ability of cancer cells to repair DNA damage caused by either unchecked growth or chemotherapy and radiation. Even though breast cancer cells can’t repair all the damage themselves, they recruit back-up DNA repair systems in the body to help damaged cells survive and continue replicating. These back-up DNA repair systems can cause previous treatments not to work if cancer returns.
“Our pre-clinical and clinical data show that a drug that can inhibit the alternate DNA repair pathway signaling may promote immune surveillance, and therefore may serve as a novel treatment option for treating breast cancer patients,” Dr. Rao said.
Based on this groundbreaking research, Virginia Kaklamani, MD, DSc, a well-known physician scientist and chair of Breast Cancer Research and Treatment, is conducting the exclusive clinical trial, which was approved by the National Cancer Institute, at the Mays Cancer Center.
“This study is a perfect example of bench to bedside initiative. We discovered that imipramine and its derivative induce DNA damage and block breast cancer cells’ ability to repair DNA. Using several pre-clinical models, our group showed that the anti-depressant imipramine can serve as a potent anti-cancer agent as well as an effective therapeutic adjuvant,” she said.
Dr. Kaklamani said before the COVID-19 pandemic, the clinical trial had approved 10 patients who began the innovative trial. “The very preliminary results are showing that imipramine is slowing down the cancer growth. The patients are tolerating the medicine very well.”
When restrictions are lifted, Dr. Kaklamani and her team plan on accruing 30 patients for this clinical trial. “COVID has thrown off everything. We are on hold now because of COVID,” she explained.
Dr. Kaklamani said although the trial was initially designed for triple negative breast cancer, the team discovered imipramine is an effective drug in estrogen receptor positive breast cancer as well. Now the trial is being opened to all newly diagnosed breast cancer patients ages 18 to 69 at the Mays Cancer Center. These are patients who have not yet had surgery.
“I’m extremely optimistic that this trial is going to show that imipramine is active in slowing down cancer cell growth and eventually we hope to use it as a preventative medication. If we could prevent breast cancer, that would be astounding. And, this is a homegrown treatment at the Mays Cancer Center that may not just treat breast cancer but prevent it from ever developing,” she said.
