Posted 8:33 a.m. Monday, October 17, 2022

New Orleans, LA – Research led by Dr. Suresh Alahari, professor of biochemistry at LSU Health New Orleans Schools of Medicine and Graduate Studies, reports that a combination of a new small molecule inhibitor and a chemotherapy drug approved by the FDA suppresses the growth of triple negative breast cancer cells synergistically. The conclusions are published in the Nature log, Oncogeneavailable here.

After reviewing the National Cancer Institute’s Diversity Set IV (a collection of compounds selected for their structural diversity and potential antitumor efficacy), the research team selected the molecule, NSC33353, as a potential antitumor compound against triple breast cancer. negative (TNBC). They tested it on human triple-negative breast cancer cells and found that it significantly suppressed cell proliferation, migration and invasion.

The researchers then turned to using the molecule in combination. Triple-negative breast cancer cells develop resistance to doxorubicin, one of the most effective chemotherapy drugs against these tumors. The researchers showed that the combination of NSC33353 and doxorubicin synergistically suppresses the growth of TNBC cells, suggesting that NSC33353 improves the sensitivity of TNBC to doxorubicin.

More common in young women, triple negative breast cancer (TNBC) represents 15 to 20% of breast cancers. It is called triple negative because these tumors lack estrogen and progesterone receptors and human epidermal growth factor receptor 2 (HER2).

“Because cancer cells don’t have these proteins, hormone therapy and drugs that target HER2 aren’t helpful,” notes Dr. Alahari.

Triple-negative breast cancer is aggressive and responds poorly to treatment, so treatment options are very limited.

“The discovery of new drugs will be of immense help for patients with TNBC,” says Dr. Alahari. “Our data indicate that the small molecule inhibitor, NSC33353, exhibits anti-tumor activity in TNBC cells and acts synergistically with a well-known chemotherapeutic agent.”

Co-authors from LSU Health New Orleans also included Hassan Yousefi, Maninder Khosla, Samuel C. Okpechi, Jessie Guidry, and Drs. Lothar Lauterboeck, David Worthylake, Jone Garai, Jovanny Zabaleta, Dorota Wyczechowska and Qinglin Yang. Mohammad Amin Zarandi and Dr. Janarthanan Jayawickramarajah of Tulane University and Dr. Joseph Kissil of H. Lee Moffitt Cancer Center also participated in the research.

The project was supported by LSU Health New Orleans School of Medicine and the Fred G. Brazda Foundation.


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