LSU Health New Orleans Newsroom

LSU Health Research Suggests Novel Combination Therapy for Triple-Negative Breast Cancer

June 29, 2022

triple negative breast cancer cells

Research led by Suresh Alahari, PhD, Professor of Biochemistry at LSU Health New Orleans schools of Medicine and Graduate Studies, suggests a combination of drugs already approved by the FDA for other cancers may be effective in treating chemo-resistant triple-negative breast cancer. The results are published in Molecular Cancer, available here.

Triple-negative breast cancer (TNBC) tumors lack estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). A subtype representing 12-55% of triple-negative breast cancer tumors has androgen receptors (AR). Since androgen receptors stimulate tumor cell progression in estrogen receptor-negative breast cancers, they have become a target of triple-negative breast cancer therapy. As well, since a substantial number of patients with triple-negative breast cancer develop resistance to paclitaxel, the FDA-approved chemotherapeutic agent for triple-negative breast cancer, new therapeutic approaches are needed.

Working in a mouse model and tissue from patients with triple-negative breast cancer, the research team screened 133 FDA-approved drugs that have a therapeutic effect against androgen receptor cells. They found that ceritinib, an FDA-approved drug for lung cancers, efficiently inhibited the growth of androgen receptor triple-negative breast cancer cells. To improve the response, they also selected enzalutamide, an FDA-approved androgen receptor antagonist for prostate cancer treatment.

“We designed a novel combinational strategy comprising enzalutamide and ceritinib to treat AR+ TNBC tumors through the dual blockade of androgen-dependent and androgen-independent AR signaling pathways,” notes Dr. Alahari.

They found that the combination of ceritinib and enzalutamide showed a robust inhibitory effect on the growth of AR+ TNBC cells. They also tested a combination of paclitaxel and ceritinib.

“The combination of paclitaxel and ceritinib showed drastic inhibition of tumor growth compared to a single drug alone,” Alahari adds. “All agents used in our study are FDA-approved, and thus the proposed combination therapy will likely be useful in the clinic.”

Triple-negative breast cancer is more prevalent in younger women, those of African and Hispanic descent, and carriers of deleterious germline mutations in the breast cancer susceptibility genes. This aggressive type accounts for 15–20% of all breast cancers.

LSU Health New Orleans co-authors included Shengli Dong, Hassan Yousefi and Samuel C. Okpechi. The team also included Isabella Van Savage, Maryl K. Wright4, Bridgette M. Collins-Burow, Matthew E Burow from Tulane University, and Margarite D. Matossian from the University of Chicago.

The research was funded by LSU Health New Orleans School of Medicine and the Fred Brazda Foundation, and the Krewe de Pink in New Orleans.

______________________________________________________________________________________________________________ LSU Health Sciences Center New Orleans (LSU Health New Orleans) educates Louisiana's health care professionals. The state's health sciences university leader, LSU Health New Orleans includes a School of Medicine with branch campuses in Baton Rouge and Lafayette, the state's only School of Dentistry, Louisiana's only public School of Public Health, and Schools of Allied Health Professions, Nursing, and Graduate Studies. LSU Health New Orleans faculty take care of patients in public and private hospitals and clinics throughout the region. In the vanguard of biosciences research, the LSU Health New Orleans research enterprise generates jobs and enormous annual economic impact. LSU Health New Orleans faculty have made lifesaving discoveries and continue to work to prevent, advance treatment or cure disease. To learn more, visit http://www.lsuhsc.edu, http://www.twitter.com/LSUHealthNO, or http://www.facebook.com/LSUHSC.

Follow Us Subscribe RSS Feed

Media Contact

Leslie Capo

Office: 504-568-4806

Cell: 504-452-9166

lcapo@lsuhsc.edu