Novel drug target discovered for triple-negative breast cancer

Novel drug target discovered for triple-negative breast cancer

Investigations led by Dr. Suresh Alahari, a professor of biochemistry in the Schools of Medicine and Graduate Studies at LSU Health New Orleans, report that a combination of a novel small inhibitor molecule and an FDA-approved chemotherapy agent synergistically suppresses the growth of triple-negative breast cancer cells. The results are published in the Nature journal Oncogene.

After screening the National Cancer Institute's Diversity Set IV (a collection of compounds selected for structural diversity and potential antitumor activity), the research team selected the molecule NSC33353 as a potential antitumor compound against triple-negative breast cancer (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 focused on combining the molecule. 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 suppressed the growth of TNBC cells, suggesting that NSC33353 increases TNBC sensitivity to doxorubicin.

Triple-negative breast cancer (TNBC) is more common in younger women and accounts for 15-20% of breast cancers. It is called triple negative because these tumors lack estrogen and progesterone receptors as well as human epidermal growth factor receptor 2 (HER2).

Because the cancer cells don’t have these proteins, hormone therapy and drugs that target HER2 are not helpful.”

Dr. Suresh Alahari, professor of biochemistry, Schools of Medicine and Graduate Studies at LSU Health New Orleans

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 great help to TNBC patients,” says Dr. Alahari. “Our data suggest that the small molecule inhibitor NSC33353 exhibits antitumor activity in TNBC cells and acts synergistically with a known chemotherapeutic agent.”

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

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

Source:

Louisiana State University Center for Health Sciences

Reference:

Yousefi, H., et al. (2022) A combination of novel NSC small molecule inhibitors together with doxorubicin inhibits triple-negative breast cancer proliferation through metabolic reprogramming. Oncogene. doi.org/10.1038/s41388-022-02497-2.

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