Inhibition of Resistant Triple-negative Breast Cancer Cells | Oncotarget
Channel: Oncotarget
Date: 2022-09-19

Dr. Balraj Singh from the Department of Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, describes a recent research paper he co-authored that was published by Oncotarget, entitled, “Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine.”
#breastcancer #authorinterview #researchpaper #openaccess #peerreview #cancer #oncology 

DOI - https://doi.org/10.18632/oncotarget.27922

Correspondence to - Anthony Lucci - alucci@mdanderson.org, and Balraj Singh - bsingh@mdanderson.org

Video transcription - https://www.oncotarget.net/2022/09/19/behind-the-study-inhibition-of-resistant-triple-negative-breast-cancer-cells/

Abstract

Highly adaptable breast cancer cells that can opportunistically switch between proliferation and quiescence are often responsible for disease relapse. We have developed a function-based selection strategy for such resistant cells, exemplified by SUM149-MA and FC-IBC02-MA triple-negative breast cancer cells. We have also reported that a lengthy treatment with low-dose 6-mercaptopurine, a clinically useful anti-inflammatory drug, inhibits such resistant cells. To more rigorously test the clinical suitability of 6-mercaptopurine, here we investigated effects of further lowering its dose and the possibility of overcoming resistance to single-drug treatment by combining the drug with another ribonucleoside analog 5-azacitidine. We found that that a lengthy treatment with 1 μM 5-azacitidine, without a significant effect on cell proliferation, sensitized cancer cells to the inhibitory effects of low-dose 6-mercaptopurine. Importantly, treatment for several weeks with low doses of 6-mercaptopurine and/or 5-azacitidine did not render cancer cells resistant to chemotherapeutic drugs doxorubicin or paclitaxel. In fact, the cells became more sensitive to chemotherapeutic drugs upon treatment with 6-mercaptopurine and/or 5-azacitidine. Our analyses of protein markers of epithelial-to-mesenchymal transition indicated that treatments with 6-mercaptopurine and/or 5-azacitidine do not significantly reverse this process in our model. Our results showed that safe drugs such as low-dose 6-mercaptopurine singly or combined with 5-azacitidine, which are suitable for use prior to disease relapse, have a potential of inhibiting highly resistant triple-negative breast cancer cells.

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Press release - https://www.oncotarget.com/news/pr/inhibition-of-resistant-triple-negative-breast-cancer-cells/

Keywords - resistant TNBC, minimal residual disease, intratumor heterogeneity, breast cancer relapse, metastasis prevention

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