NF-κB, stem cells and breast cancer: the links get stronger

Self-renewing breast cancer stem cells are key actors in perpetuating tumour existence and in treatment resistance and relapse. The molecular pathways required for their maintenance are starting to be elucidated. Among them is the transcription factor NF-κB, which is known to play critical roles in cell survival, inflammation and immunity. Recent studies indicate that mammary epithelial NF-κB regulates the self-renewal of breast cancer stem cells in a model of Her2-dependent tumourigenesis. We will describe here the NF-κB-activating pathways that are involved in this process and in which progenitor cells this transcription factor is actually activated

Targeting breast cancer stem cells

The cancer stem cell (CSC) hypothesis postulates that tumors are maintained by a self‐renewing CSC population that is also capable of differentiating into non‐self‐renewing cell populations that constitute the bulk of the tumor. Although, the CSC hypothesis does not directly address the cell of origin of cancer, it is postulated that tissue‐resident stem or progenitor cells are the most common targets of transformation. Clinically, CSCs are predicted to mediate tumor recurrence after chemo‐ and radiation‐therapy due to the relative inability of these modalities to effectively target CSCs. If this is the case, then CSC must be efficiently targeted to achieve a true cure. Similarities between normal and malignant stem cells, at the levels of cell‐surface proteins, molecular pathways, cell cycle quiescence, and microRNA signaling present challenges in developing CSC‐specific therapeutics. Approaches to targeting CSCs include the development of agents targeting known stem cell regulatory pathways as well as unbiased high‐throughput siRNA or small molecule screening. Based on studies of pathways present in normal stem cells, recent work has identified potential “Achilles heals” of CSC, whereas unbiased screening provides opportunities to identify new pathways utilized by CSC as well as develop potential therapeutic agents. Here, we review both approaches and their potential to effectively target breast CSC.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135704/1/mol2201045404.pd

Breast cancer stem cells: implications for therapy of breast cancer

The concept of cancer stem cells responsible for tumour origin, maintenance, and resistance to treatment has gained prominence in the field of breast cancer research. The therapeutic targeting of these cells has the potential to eliminate residual disease and may become an important component of a multimodality treatment. Recent improvements in immunotherapy targeting of tumour-associated antigens have advanced the prospect of targeting breast cancer stem cells, an approach that might lead to more meaningful clinical remissions. Here, we review the role of stem cells in the healthy breast, the role of breast cancer stem cells in disease, and the potential to target these cells

Chemoresistance in breast cancer stem cells

Breast cancer is the most prevalent cancer in women worldwide, contributing to 14% of all new cancer cases and 6.8% of all cancer deaths in 2014. A new area of cancer research has arisen from the discovery of cancer cells with stem cell-like proper ties in several tumor types including the colon, head and breast. Cancer stem cells, which are undifferentiated cells, have the ability of self-renewal, self-replication and differentiating into malignant daughter cells. Breast tumor s containing breast cancer stem cells have increased resistance to chemo- and r adiotherapy, a higher relapse r ate and increased susceptibility to metastasis. Potential targets for the treatment of chemoresistance include signaling pathways of breast cancer stem cells such as the -catenin-, Notch and Hedgehog pathways. Chemoresistance of these breast cancer stem cells potentially elucidates failure to achieve complete remission post-therapy, and, thus, relapses of breast cancer. By unraveling the mechanism behind the chemotherapeutic resistance of breast cancer stem cells, researchers could develop more efficient treatment strategies towards breast cancer.The Medical Research Council of South Africa, the Cancer Association of South Africa, National Research Foundation and the Struwig-Germeshuysen Cancer Research trust of South Africa.http://www.biomedres.infoam2017Physiolog

Upregulation of the Oct3/4 network in basal breast cancer is associated with its metastatic potential and shows tissue dependent variability

Adaptive plasticity of Breast Cancer stem cells (BCSCs) is strongly correlated with cancer progression and resistance, leading to a poor prognosis. In this study, we report the expression profile of several pioneer transcription factors of th

Endocrine therapy: defining the path of least resistance

One of the best-characterized oncogenic mechanisms in breast cancer is the aberrant activation of phosphatidylinositol-3-kinase, protein kinase B, and mammalian target of rapamycin signaling. In both endocrine-resistant disease and breast cancer stem cells, this is commonly caused by specific genetic lesions or amplification of key pathway components or both. These observations have generated two interesting hypotheses. Firstly, do these genetic anomalies provide clinically significant biomarkers predictive of endocrine resistance? Secondly, do tamoxifen-resistant breast cancer cells emerge from a stem-like cell population? New studies, published in Breast Cancer Research, raise the possibility that these hypotheses are intrinsically linked