Abstract
Triple-negative breast cancer (TNBC) is defined by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). It is unresponsive to targeted therapy and is associated with a high degree of malignancy, a high propensity for metastasis, high recurrence rates, and poor prognosis. In the modern concept of cancer biology, a subset of cancer cells known as tumor-initiating cells or cancer stem cells (CSCs) are defined as essential for the development and dissemination of cancer. These are a population of highly tumorigenic and self-renewing pluripotent cells that are inherently associated to the initiation, dissemination, relapse, and development of drug resistance. Specifically, some cell signaling pathways may affect the ability of CSCs to self-renew, differentiate, proliferate, and survive. To guide future research, in this review, we address compounds that target cell signaling and eliminate TNBC stem cells. Potential translational inhibitors of the Hedgehog, nuclear factor κB (NF-κB), Wnt, Notch, Hippo, TGF-β, JAK/STAT, and PI3K/AKT/mTOR cell signaling pathways are discussed, with a focus on TNBC stem cell eradication.