Fultang Norman, Chakraborty Madhuparna, Peethambaran Bela
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19140, USA.
Department of Biological Sciences, The University of the Sciences, Philadelphia, PA 19140, USA.
Cancer Drug Resist. 2021 Jun 19;4(2):321-342. doi: 10.20517/cdr.2020.106. eCollection 2021.
Triple Negative Breast Cancer (TNBC) is the most lethal subtype of breast cancer. Despite the successes of emerging targeted therapies, relapse, recurrence, and therapy failure rates in TNBC significantly outpace other subtypes of breast cancer. Mounting evidence suggests accumulation of therapy resistant Cancer Stem Cell (CSC) populations within TNBCs contributes to poor clinical outcomes. These CSCs are enriched in TNBC compared to non-TNBC breast cancers. The mechanisms underlying CSC accumulation have been well-characterized and discussed in other reviews. In this review, we focus on TNBC-specific mechanisms that allow the expansion and activity of self-renewing CSCs. We highlight cellular signaling pathways and transcription factors, specifically enriched in TNBC over non-TNBC breast cancer, contributing to stemness. We also analyze publicly available single-cell RNA-seq data from basal breast cancer tumors to highlight the potential of emerging bioinformatic approaches in identifying novel drivers of stemness in TNBC and other cancers.
三阴性乳腺癌（TNBC）是乳腺癌中最致命的亚型。尽管新兴的靶向治疗取得了成功，但TNBC的复发、再发和治疗失败率显著高于其他乳腺癌亚型。越来越多的证据表明，TNBC中治疗抗性癌症干细胞（CSC）群体的积累导致了不良的临床结果。与非TNBC乳腺癌相比，这些CSC在TNBC中更为富集。CSC积累的潜在机制在其他综述中已有充分描述和讨论。在本综述中，我们关注TNBC特异性机制，这些机制允许自我更新CSC的扩增和活性。我们强调细胞信号通路和转录因子，特别是在TNBC中比非TNBC乳腺癌更富集，它们有助于维持干性。我们还分析了来自基底样乳腺癌肿瘤的公开单细胞RNA测序数据，以突出新兴生物信息学方法在识别TNBC和其他癌症中干性新驱动因素方面的潜力。
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