Certain therapies that have proven effective in treating some types of breast cancers are ineffective for women diagnosed with triple-negative breast cancer (TNBC). In fact, there is limited targeted drug therapy for this type of breast cancer 鈥� the most aggressive type, diagnosed in about 20 percent of breast cancer patients.
But a new by University of 91吃瓜 researcher and collaborators, published in Nature Communications, shows that an existing, FDA-approved drug that treats other types of breast cancer may work for TNBC.听
Zhang, the Dee Associate Professor of and faculty member of the , discovered that TNBC cells may be vulnerable to a targeted therapy after his team used a whole-genome screening method that evaluated 27,000 genes at once. Unexpectedly, they identified that one gene, the death effector domain-containing (DEDD) gene, makes multiple copies of itself in more than 60 percent of TNBC tumors. Regular cells contain only two copies.
鈥淏ecause the tumor expressed a very high level of this gene, we knew that the gene must do something, because evolutionarily the cell just doesn鈥檛 need that many copies,鈥� Zhang said. 鈥淭here鈥檚 no reason for it to be there; it鈥檚 inefficient.鈥�
The gene acts essentially like a spark plug in a car, encouraging it to run, and the cell becomes addicted to the protein the DEDD gene releases. 鈥淭he cell needs to consume more and more, but it also makes the cells very vulnerable,鈥� Zhang said, likening the process to a person who is addicted to drugs.
Traditional therapies for breast cancer include radiation therapy, chemotherapy聽or surgery, which have been the primary options for treating TNBC.听More recently, gene-based, targeted therapy has been added to the mix for other types of breast cancer. Targeted anti-cancer therapy allows researchers to tackle one feature of a cancer cell that makes it vulnerable to a drug, but which other, 鈥渘ormal鈥� cells聽don鈥檛 have. 鈥淭argeted therapy works really well, and everybody tries to find unique markers for each type of cancer, so the drug therapy can target it,鈥� Zhang said. 鈥淏ut triple-negative breast cancer is a type that doesn鈥檛 have a clear marker yet.鈥�
Zhang鈥檚 research showed that one of the targeted drugs used to treat other types of breast cancer, called a CDK4/6 inhibitor, combined with another FDA-approved anti-cancer drug, an聽EGFR/HER2 inhibitor, killed TNBC cells.
Researchers may take the information from Zhang鈥檚 study to begin clinical trials, or, because the drug is already FDA-approved, offer the new treatment off-label.
Repurposing FDA-approved drugs for new patient groups is one of Zhang鈥檚 passions聽and what he looks toward when designing his mechanistic studies of how cancer cells live and die. Treatment using a repurposed drug is faster to implement because new drugs may not be available for years, but 鈥渇or repurposed drugs, we already have a safety profile out there, and know how they work in certain tissue context,鈥� Zhang said.
In addition to Zhang, collaborators included Yingjia Ni, Keon R. Schmidt, Barnes A. Werner, Jenna K. Koenig, Ian H. Guldner, Patricia M. Schnepp, Xuejuan Tan, Lan Jiang, Misha Host, Longhua Sun, Erin N. Howe聽and Junmin Wu, all from 91吃瓜 and the Harper Cancer Research Institute. Also contributing were Laurie E. Littlepage of 91吃瓜, the Harper Cancer Research Institute and Indiana University Melvin and Bren Simon Cancer Center, and Harikrishna Nakshatri of the Indiana University Melvin and Bren Simon Cancer Center, as well as the departments of surgery, biochemistry and molecular biology at the Indiana University School of Medicine.
The study was funded as part of the Breast Cancer Research Program Breakthrough Award through the Department of Defense, and partially supported by the National Institutes of Health and the Indiana Clinical and Translational Sciences Institute.听
Originally published by at on July 23.