Trending with Impact: Combination Therapeutics Inhibit Breast Cancer Resistance

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June 18, 2021

Oncotarget published this trending research paper on March 30, 2021, entitled, "Inhibition of resistant triple-negative breast cancer cells with low-dose 6-mercaptopurine and 5-azacitidine" by researchers from the University of Texas MD Anderson Cancer Center, Houston, Texas. 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 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. To date, this research paper has generated an Altmetric Attention Score of 49. The Altmetric Attention Score provides an at-a-glance indication of the volume and type of online attention the research has received. Top Oncotarget publications rated by Altmetric Attention Score - https://www.oncotarget.com/news/altmetric/ Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.27922 DOI - https://doi.org/10.18632/oncotarget.27922 Full text - https://www.oncotarget.com/article/27922/text/ Correspondence to - Anthony Lucci - alucci@mdanderson.org and Balraj Singh - bsingh@mdanderson.org Keywords - resistant TNBC, minimal residual disease, intratumor heterogeneity, breast cancer relapse, metastasis prevention About Oncotarget Oncotarget is a bi-weekly, peer-reviewed, open access biomedical journal covering research on all aspects of oncology. To learn more about Oncotarget, please visit https://www.oncotarget.com or connect with: SoundCloud - https://soundcloud.com/oncotarget Facebook - https://www.facebook.com/Oncotarget/ Twitter - https://twitter.com/oncotarget YouTube - https://www.youtube.com/c/OncotargetYouTube/ LinkedIn - https://www.linkedin.com/company/oncotarget Pinterest - https://www.pinterest.com/oncotarget/ Reddit - https://www.reddit.com/user/Oncotarget/ Oncotarget is published by Impact Journals, LLC please visit https://www.ImpactJournals.com or connect with @ImpactJrnls Media Contact MEDIA@IMPACTJOURNALS.COM 18009220957

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