Cancer stem cells impact heterogeneity and uncertainty pdf

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cancer stem cells impact heterogeneity and uncertainty pdf

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Cancer stem cells in the development of liver cancer

Oncotarget a primarily oncology-focused, peer-reviewed, open access, biweekly journal aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Its scope is unique. The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial , Introducing OncoTarget. Sponsored Conferences. Impact Journals is a member of the Society for Scholarly Publishing.

Cancer stem cells CSCs are subpopulations of cells with stem cell characteristics that produce both cancerous and non-tumorigenic cells in tumor tissues. The literature reports that CSCs are closely related to the development of hepatocellular carcinoma HCC and promote the malignant features of HCC such as high invasion, drug resistance, easy recurrence, easy metastasis, and poor prognosis. This review discusses the origin, molecular, and biological features, functions, and applications of CSCs in HCC in recent years; the goal is to clarify the importance of CSCs in treatment and explore their potential value in HCC-targeted therapy. CSCs have the capacity to self-renew and differentiate into heterogeneous tumor cells, which are responsible for the maintenance and propagation of the tumor Batlle and Clevers, Basing on this breakthrough, CSCs were subsequently found in a variety of hematopoietic cancer and solid tumors. Hepatocellular carcinoma accounts for most of the incidence of primary liver cancer, and the existence of CSCs has been demonstrated through the identification of several surface markers in HCC Machida,

Tissues with defined cellular hierarchies in development and homeostasis give rise to tumors with cellular hierarchies, suggesting that tumors recapitulate specific tissues and mimic their origins. Glioblastoma GBM is the most prevalent and malignant primary brain tumor and contains self-renewing, tumorigenic cancer stem cells CSCs that contribute to tumor initiation and therapeutic resistance. As normal stem and progenitor cells participate in tissue development and repair, these developmental programs re-emerge in CSCs to support the development and progressive growth of tumors. Elucidation of the molecular mechanisms that govern CSCs has informed the development of novel targeted therapeutics for GBM and other brain cancers. CSCs are not self-autonomous units; rather, they function within an ecological system, both actively remodeling the microenvironment and receiving critical maintenance cues from their niches. To fulfill the future goal of developing novel therapies to collapse CSC dynamics, drawing parallels to other normal and pathological states that are highly interactive with their microenvironments and that use developmental signaling pathways will be beneficial.

Cancer stem cells: impact, heterogeneity, and uncertainty.

The identification of cancer stem cells CSCs that are responsible for tumor initiation, growth, metastasis, and therapeutic resistance might lead to a new thinking on cancer treatments. Similar to stem cells, CSCs also display high resistance to radiotherapy and chemotherapy with genotoxic agents. Thus, conventional therapy may shrink the tumor volume but cannot eliminate cancer. Eradiation of CSCs represents a novel therapeutic strategy. In addition to the protein kinases and enzymes that are involved in DDR, other processes that affect the DDR including chromatin remodeling should also be explored.

The cancer stem cell CSC hypothesis has been disproved in many cancers. Hepatocytes gave rise to HCC. Several groups have demonstrated that oval cells or liver progenitor cells give rise to TICs. The definition of CSCs includes pluripotency, while TICs do not have to have pluripotency and only need to have bi- or multipotential to give rise to diverse tumor types and tumor initiation potential in mouse models. Stem cells proliferate via self-renewing division in which the two daughter cells differ in proliferative potential, with one displaying differentiated phenotype and the other retaining self-renewing activity.

It has been proposed that a subpopulation of tumour cells with stem cell-like characteristics, known as cancer stem cells CSCs , drives tumour initiation and generates tumour heterogeneity, thus leading to cancer metastasis, recurrence, and drug resistance. Although there has been substantial progress in CSC research into many solid tumour types, an understanding of the biology of CSCs in lung cancer remains elusive, mainly because of their heterogeneous origins and high plasticity. Here, we demonstrate that engineered lung cancer cells derived from normal human airway basal epithelial cells possessed CSC-like characteristics in terms of multilineage differentiation potential and strong tumour-initiating ability. Moreover, we established an in vitro 3D culture system that allowed the in vivo differentiation process of the CSC-like cells to be recapitulated. This engineered CSC model provides valuable opportunities for studying the biology of CSCs and for exploring and evaluating novel therapeutic approaches and targets in lung CSCs. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

A novel model of liver cancer stem cells developed from induced pluripotent stem cells

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The relationships between cancer and stemness have a long history that is traced here. From the midth century when the first theory on the embryonic origin of cancer was formulated to works on embryonal carcinoma cells in the midth century, many steps have been crossed leading to the current cancer stem cell theory postulating that tumor growth is supported by a small fraction of the tumoral cells that have stem-like properties. However, in the last fifteen years, many works regularly encourage us to revise the concept of cancer stem cell. This article mentions key results that lead to a new perspective where cancer stem cells are primarily seen as cells exhibiting increased epigenetic plasticity and increased gene expression variability. This perspective suggests new therapeutical interventions consisting in stabilizing gene expression to control cancer cell proliferation and prevent stochastic gene expression variations that could lead to therapeutic resistance.

Cancer Stem Cells: A Potential Breakthrough in HCC-Targeted Therapy

Journal of Oncology

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Cancer Stem Cells: From Historical Roots to a New Perspective

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