The cancer stem cell (CSC) hypothesis postulates that cancer originates from the malignant transformation of stem cells and is considered to apply to a variety of cancers. Additionally, cancer cells alter metabolic processes to sustain their characteristic uncontrolled growth and proliferation. Further, microRNAs (miRNAs) are found to be involved in acquisition of stem cell-like properties, regulation and reprogramming of cancer cells during cancer progression through its post-transcriptional-regulatory activity. In this concise review, we aim to integrate the current knowledge and recent advances to elucidate the mechanisms involved in the regulation of cell reprogramming and highlights the potential therapeutic implications for the future.

Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called \"cancer stem cells\". Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.

Cancer stem cells (CSCs) comprise the subpopulation of tumor bulk and acquire resistant to conventional therapies and are considered as the primary tumor initiator cells. Nowadays, the tumor heterogeneity originated from CSCs, and its progenitors are accepted as a mortifying drawback in front of the cancer therapies. However, escalating knowledge gained from studies investigating the biology of CSCs will open up new frames for targeted therapies and decrease the chance of recurrence of the disease. In this review, the general understanding of CSCs and current studies were discussed briefly. Considering the latest data collected from studies of CSCs, defining the tumor heterogeneity and tumor microenvironment comprehensively will be very important to step up the cancer research.

BACKGROUND: Cancer stem cells (CSCs) mediate tumor initiation and maintenance. These cells are chemoresistant and possess characteristics such as self-renewal, pluripotency, plasticity and differentiation. They have aberrant or altered signaling pathways depending on tumor microenvironment, tumor type, etc. CSCs are responsible for highly aggressive and invasive form of the disease following chemo- and/or radiotherapy. Eliminating CSCs is likely to improve the survival rate in patients. Several anti-CSC strategies and associated targets have been proposed and validated till date. Areas covered: The main emphasis is on the patent applications/patents filed/granted in the last few years (2012-2015). The anti-CSC agents are discussed under two broad headings - small- and macromolecules. Different subclasses are further elaborated, e.g., kinase inhibitors, polypeptides, etc. Expert opinion: Clinical development of small- and macromolecular anti-CSC therapeutics is underway. Few of these agents act on validated targets such as kinases. Potential problems with these agents can be envisaged based on our understanding of target biology. Other issues governing the choice of small- versus macromolecules include druggability of the target, ease of its modulation and the presence of compensatory mechanisms. Drug repurposing can be attempted to discover newer anti-CSC drugs quickly.

BACKGROUND: CD133 is one of the most commonly used markers of cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CD133 in gastric cancer remains controversial. To clarify a precise determinant of the clinical significance of CD133, we conducted a systematic review and meta-analysis to elucidate the correlation of CD133 overexpression with prognosis and clinicopathological features of GC patients.
METHODS: A search in the Cochrane Library, PubMed, Medline, Web of Knowledge and Chinese CNKI, CBM (up to Jun 30, 2015) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies, and then RevMan 5.2.0 software was used for meta-analysis.
RESULTS: A total of 603 gastric cancer patients from 8 studies were included. The results of the meta-analyses showed that, there were significant differences of CD133 expression in the following comparisons: gastric cancer tissues vs. normal esophageal tissue (OR = 3.49, 95% CI [2.48, 490], P < 0.00001), lymph node metastasis vs. non-lymph node metastasis (OR = 2.75, 95% CI [1.99, 3.81], P < 0.00001), distant metastasis vs. non-distant metastasis (OR = 2.38, 95%CI [1.47, 3.85], P < 0.0004), clinical stages III~IV vs. clinical stages I~II (OR = 2.83, 95% CI [2.13, 3.76], P < 0.00001), as well as the accumulative 5-year overall survival rates of CD133-positive vs. CD133-negative patients (OR = 0.23, 95% CI [0.16, 0.33], P < 0.00001).
CONCLUSIONS: Overexpression of CD133 is associated with lymph node metastasis, distant metastasis, poor TNM stage. Additionally, CD133-positive gastric cancer patients had worse prognosis. Our results indicate that CD133 may be involved in the carcinogenesis of gastric cancer. Evaluation of cytoplasmic CD133 overexpression in gastric cancer tissue sections may be useful in the future as a novel prognostic factor. Nevertheless, due to the poor quality and small sample size of included trials, more well-designed multi-center randomized controlled trials should be performed.

Soy isoflavones are dietary components for which an association has been demonstrated with reduced risk of prostate cancer (PCa) in Asian populations. However, the exact mechanism by which these isoflavones may prevent the development or progression of PCa is not completely understood. There are a growing number of animal and in vitro studies that have attempted to elucidate these mechanisms. The predominant and most biologically active isoflavones in soy products, genistein, daidzein, equol, and glycetin, inhibit prostate carcinogenesis in some animal models. Cell-based studies show that soy isoflavones regulate genes that control cell cycle and apoptosis. In this review, we discuss the literature relevant to the molecular events that may account for the benefit of soy isoflavones in PCa prevention or treatment. These reports show that although soy isoflavone-induced growth arrest and apoptosis of PCa cells are plausible mechanisms, other chemo protective mechanisms are also worthy of consideration. These possible mechanisms include antioxidant defense, DNA repair, inhibition of angiogenesis and metastasis, potentiation of radio- and chemotherapeutic agents, and antagonism of estrogen- and androgen-mediated signaling pathways. Moreover, other cells in the cancer milieu, such as the fibroblastic stromal cells, endothelial cells, and immune cells, may be targeted by soy isoflavones, which may contribute to soy-mediated prostate cancer prevention. In this review, these mechanisms are discussed along with considerations about the doses and the preclinical models that have been used.

Accumulating evidence suggests that self-renewal and differentiation capabilities reside only in a subpopulation of tumor cells, termed cancer stem cells (CSCs), whereas the remaining tumor cell population lacks the ability to initiate tumor development or support continued tumor growth. In head and neck squamous cell carcinoma (HNSCC), as with other malignancies, CSCs have been increasingly shown to have an integral role in tumor initiation, disease progression, metastasis, and treatment resistance. In this article, the author summarizes the current knowledge of the role of CSCs in HNSCC and discusses the therapeutic implications and future directions of this field.