Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade, Serbia.
Cells. 2019 Aug 22;8(9):957. doi: 10.3390/cells8090957.
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.
三阴性乳腺癌（TNBC）因其高度异质性、侵袭性和缺乏治疗选择而成为最致命的乳腺癌亚型。化疗仍然是 TNBC 治疗的标准护理，但不幸的是，患者经常会产生耐药性。因此，近年来，人们已经做出了巨大的努力来阐明 TNBC 化疗耐药的机制，以期确定新的分子靶点。很明显，TNBC 化疗耐药的发展是多方面的，基于肿瘤微环境、药物外排、癌症干细胞和肿瘤细胞的精心相互作用。多种信号通路的改变控制着这些相互作用。此外，TNBC 的高度异质性，表现在存在几种分子特征上，这给成功治疗带来了重大障碍。在目前的深入综述中，我们探讨了关键机制对 TNBC 化疗耐药的贡献以及克服这些机制的新兴策略。我们讨论了靶向这些机制成分的新型抗肿瘤药物，并特别关注它们目前的临床开发情况，同时强调了成功管理 TNBC 仍然面临的挑战。本综述中提出的证据概述了化疗治疗后 TNBC 存活中关键途径的作用，并强调了在临床研究中使用联合药物策略和纳入生物标志物的重要性。
