Systems and Network Pharmacology Approaches to Cancer Stem Cells Research and Therapy.
Systems and Network Pharmacology Approaches to Cancer Stem Cells Research and Therapy.
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DOI：
10.4172/2157-7633.s7-005
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发表时间：
2012
期刊：
影响因子：
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通讯作者：
I. Muqbil;Ginny W. Bao;Rkya El-Kharraj;M. Shah;R. Mohammad;F. Sarkar;A. Azmi
中科院分区：
文献类型：
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作者：
I. Muqbil;Ginny W. Bao;Rkya El-Kharraj;M. Shah;R. Mohammad;F. Sarkar;A. Azmi
癌症干细胞（CSC）假说越来越多地被接受为一个模型来解释在实体瘤中常见的功能异质性。根据这一假设，肿瘤内存在细胞的分层组织，其中干细胞样细胞的差异亚群负责肿瘤生长的维持和复发。CSC已被证明存在于各种实体瘤中，特别是具有已知耐药表型的实体瘤，如乳腺癌、前列腺癌和胰腺癌（PDAC）。在所有这些模型中，三个关键途径的放松管制的共性正在显现; Wnt，notch和hedgehog维持CSC自我更新能力。总的来说，这些主要途径与观察到的CSC对化疗和放疗的抗性有关。现有的知识缺乏和我们对与CSC相关的分子特征的不完全理解突出了在分离和鉴定与这些细胞相关的独特途径方面需要更好的方法。在这个方向上，计算生物学，特别是系统和网络方法，已被证明是非常有用的解开途径的复杂性，如与CSC相关的。重点介绍了最新的分子，网络，细胞，临床和治疗癌症的研究结果，这篇文章倾向于提供丰富的见解系统和网络生物学方法CSC标志物识别，通过它们逃避治疗的机制以及治疗方法，这将有助于征服这些难以捉摸的细胞在不可治愈和难治性恶性肿瘤。
The cancer stem cell (CSC) hypothesis is increasingly being accepted as a model to explain for the functional heterogeneity that is commonly observed in solid tumors. According to this hypothesis, there exists a hierarchical organization of cells within the tumor, in which a differential subpopulation of stem-like cells is responsible for sustaining and recurrence of tumor growth. CSCs have been shown to exist in a variety of solid tumors especially those with known resistant phenotypes such as breast, prostate and pancreatic adenocarcinoma (PDAC). In all these models, the commonality of deregulation of three crucial pathways; Wnt, notch and hedgehog that maintain CSC self-renewal capacity is emerging. Collectively these major pathways and have been linked to the observed resistance of CSC to chemotherapy and radiotherapy. The existing lack of knowledge and our incomplete understanding of the molecular signatures associated with CSCs highlight the need for better approaches in both isolation and identification of unique pathways associated with these cells. In this direction, computational biology, especially systems and network approaches, have proven to be of great utility in unraveling pathway complexities such as those associated with CSCs. With highlights on the most up-to-date molecular, network, cellular, clinical, and therapeutic cancer research findings, this article tends to provide a wealth of insights on systems and network biology approaches to CSC marker identification, the mechanism through which they evade treatment as well as therapeutic approaches that will help in conquering these elusive cells in incurable and refractory malignancies.