Muqbil Irfana, Bao Ginny W, El-Kharraj Rkya, Shah Minjel, Mohammad Ramzi M, Sarkar Fazlul H, Azmi Asfar S
Department of Biochemistry, Aligarh Muslim University, Aligarh, Uttar Pradesh, India.
J Stem Cell Res Ther. 2012 Dec 16;Suppl 7(5). doi: 10.4172/2157-7633.S7-005.
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.
癌症干细胞（CSC）假说越来越被认为是一种解释实体瘤中常见功能异质性的模型。根据这一假说，肿瘤内部存在细胞的分层组织，其中一种不同的干细胞样细胞亚群负责维持肿瘤生长和复发。已证明CSC存在于多种实体瘤中，尤其是那些具有已知耐药表型的肿瘤，如乳腺癌、前列腺癌和胰腺腺癌（PDAC）。在所有这些模型中，维持CSC自我更新能力的三个关键信号通路（Wnt、Notch和Hedgehog）失调的共性正在显现。总体而言，这些主要信号通路与观察到的CSC对化疗和放疗的耐药性有关。目前对与CSC相关的分子特征缺乏了解且认识不完整，这凸显了在分离和鉴定与这些细胞相关的独特信号通路方面需要更好的方法。在这个方向上，计算生物学，尤其是系统和网络方法，已被证明在揭示与CSC相关的信号通路复杂性等方面非常有用。本文重点介绍了最新的分子、网络、细胞、临床和治疗癌症研究结果，旨在就CSC标志物鉴定的系统和网络生物学方法、它们逃避治疗的机制以及有助于攻克不可治愈和难治性恶性肿瘤中这些难以捉摸的细胞的治疗方法提供丰富的见解。
