<p>Targeting stem cells in the realm of drug-resistant breast cancer</p>

Abstract

Since its first documentation, breast cancer (BC) has been a conundrum that ails millions of women every year. This cancer has been well studied by researchers all over the world, which has improved the patient outcome significantly. There are many diagnostic markers to identify the disease, but early detection and then subclassification of this cancer remain dubious. Even after the correct diagnosis, more than half the patients come back with a more aggressive and metastatic tumor. The underpinning mechanism that governs the resistance includes over-amplification of receptors, mutations in key gene targets, and activation of different signaling. A plethora of drugs have been devised that have shown promising results in clinical settings. However, in recent times, the role played by cancer stem cells in disease progression and their interaction in mediating the resistance to cellular insults have come into the limelight. As breast cancer stem cells (BCSCs) are dormant in nature, it is highly likely that they fail to directly respond to the cytotoxic drugs which are meant for ablating rapidly proliferating cells. Furthermore, the absence of well-characterized, drug-able surface markers to date, has limited the application of targeted therapies in complete eradication of the disease. In this review, our intent is to discuss versatile therapeutics in practice followed by discussing the upcoming therapy strategies in the pipeline for BC. Furthermore, we focus on the roles played by BCSCs in mediating the resistance, and therefore, the aspects of new therapeutics against BCSCs under development that may ease the burden in future has also been discussed.

Ginsenoside panaxatriol reverses TNBC paclitaxel resistance by inhibiting the IRAK1/NF-κB and ERK pathways

“…In turn, these factors activate inflammation related signaling pathways such as NF-κB and signal transducer and activator of transcription 3 (STAT3) (Wang et al, 2018;Wong, Che & Leung, 2015;Yue et al, 2006), which further promote cell survival through regulating apoptosis proteins and promote the formation of CSC through regulating CSC related genes (Rhyasen et al, 2013). Importantly, in accordance to IL-8 inhibitor, anti-IL6 antibody, anti-CXCL1 antibody, or anti-CCL2 antibody, here we showed that target IRAK1 mediated pathways by GPT can effectively down-regulate these cytokines and disrupt this process (Dey, Rathod & De, 2019;Heo, Wahler & Suh, 2016;Miyake et al, 2019;Teng et al, 2017).…”

Breast cancer stem cell RNA‑pulsed dendritic cells enhance tumor cell killing by effector T�cells�

“…A subpopulation of cells in tumors exhibit stem cell properties, including dormancy, self-renewal, infinite proliferation and multi-lineage differentiation (4,5). Studies in various types of cancer, in particular BC, have demonstrated that cancer stem cells (CSCs) subpopulations play a role in cancer recurrence, therapy resistance, metastasis and aggressive relapse (6)(7)(8). Therefore, CSCs are becoming important targets for cancer therapy (8,9).…”

“…Studies in various types of cancer, in particular BC, have demonstrated that cancer stem cells (CSCs) subpopulations play a role in cancer recurrence, therapy resistance, metastasis and aggressive relapse (6)(7)(8). Therefore, CSCs are becoming important targets for cancer therapy (8,9). In a number of studies investigating BC, distinct cell subpopulations with high tumorigenicity and stem cell properties have been isolated (10,11).…”

Combination of Docetaxel with Thymoquinone in Nanoemulsion Impedes the Migration of Breast Cancer Stem Cells

“…3 As most standard therapeutic agents are proposed mainly to interfere with rapidly dividing cells, these tumorigenic stem cells would be highly resistant to chemotherapy. 4 Therefore, it is necessary to find effective new therapeutic approaches that have the ability to control local metastasis by targeting the BCSC and overcome the major limitations of traditional therapy. Greener synthesis and fabrication of nanomaterials recently have gained growing attention due to their exclusive characteristics towards biomedical applications as an alternative to overcome the toxic effects of conventional therapy.…”