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Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge

Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia
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Cells 2019, 8(9), 957; https://doi.org/10.3390/cells8090957
Received: 8 August 2019 / Accepted: 21 August 2019 / Published: 22 August 2019
(This article belongs to the Special Issue Molecular and Cellular Mechanisms of Cancers: Breast Cancer)
Triple-negative (TNBC) is the most lethal subtype of breast cancer owing to high heterogeneity, aggressive nature, and lack of treatment options. Chemotherapy remains the standard of care for TNBC treatment, but unfortunately, patients frequently develop resistance. Accordingly, in recent years, tremendous effort has been made into elucidating the mechanisms of TNBC chemoresistance with the goal of identifying new molecular targets. It has become evident that the development of TNBC chemoresistance is multifaceted and based on the elaborate interplay of the tumor microenvironment, drug efflux, cancer stem cells, and bulk tumor cells. Alterations of multiple signaling pathways govern these interactions. Moreover, TNBC’s high heterogeneity, highlighted in the existence of several molecular signatures, presents a significant obstacle to successful treatment. In the present, in-depth review, we explore the contribution of key mechanisms to TNBC chemoresistance as well as emerging strategies to overcome them. We discuss novel anti-tumor agents that target the components of these mechanisms and pay special attention to their current clinical development while emphasizing the challenges still ahead of successful TNBC management. The evidence presented in this review outlines the role of crucial pathways in TNBC survival following chemotherapy treatment and highlights the importance of using combinatorial drug strategies and incorporating biomarkers in clinical studies. View Full-Text
Keywords: triple-negative breast cancer; chemoresistance; ABC transporters; cancer stem cells; signaling pathways; hypoxia; apoptosis; receptor tyrosine kinases; microRNA; molecular subtypes triple-negative breast cancer; chemoresistance; ABC transporters; cancer stem cells; signaling pathways; hypoxia; apoptosis; receptor tyrosine kinases; microRNA; molecular subtypes
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Nedeljković, M.; Damjanović, A. Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge. Cells 2019, 8, 957.

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