Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell.
Tumor heterogeneity of gastric cancer: From the perspective of tumor-initiating cell.
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DOI：
10.3748/wjg.v24.i24.2567
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发表时间：
2018-06-28
影响因子：
4.3
通讯作者：
Zhu ZG
中科院分区：
文献类型：
--
作者：
Gao JP;Xu W;Liu WT;Yan M;Zhu ZG
胃癌（GC）仍然是最常见和恶性的癌症类型之一，由于其快速进展，远处转移，并对常规化疗耐药，尽管已经努力了解这种耐药的潜在机制并改善临床结果。肿瘤的异质性是恶性肿瘤的基本特征，在肿瘤的发生发展和耐药性中起着重要作用。肿瘤起始细胞（TIC）模型已被提出来解释GC的遗传，组织学和表型异质性。TIC占肿瘤细胞的次要亚群，其关键特征包括高致瘤性、维持自我更新潜力、产生致瘤性和非致瘤性癌细胞以及对化疗的抗性。关于GC肿瘤起始细胞（GATIC），已经进行了大量研究以（1）鉴定用于GATIC纯化和功能验证的推定特异性细胞标记物;（2）追踪GATIC的起源;（3）解码GATIC的调节机制。此外，最近的研究表明GATIC的可塑性和GATIC与其周围因素（TIC生态位或肿瘤微环境）之间的相互作用。所有这些研究为GATIC靶向治疗的发展铺平了道路，该治疗处于临床前研究和临床试验阶段。本文通过对上述GATICs的基础和临床研究的回顾，从TIC的角度对GC的异质性进行解释。在GATIC调查过程中遇到的问题和潜在的解决方案进行了讨论。
Gastric cancer (GC) remains one of the most common and malignant types of cancer due to its rapid progression, distant metastasis, and resistance to conventional chemotherapy, although efforts have been made to understand the underlying mechanism of this resistance and to improve clinical outcome. It is well recognized that tumor heterogeneity, a fundamental feature of malignancy, plays an essential role in the cancer development and chemoresistance. The model of tumor-initiating cell (TIC) has been proposed to explain the genetic, histological, and phenotypical heterogeneity of GC. TIC accounts for a minor subpopulation of tumor cells with key characteristics including high tumorigenicity, maintenance of self-renewal potential, giving rise to both tumorigenic and non-tumorigenic cancer cells, and resistance to chemotherapy. Regarding tumor-initiating cell of GC (GATIC), substantial studies have been performed to (1) identify the putative specific cell markers for purification and functional validation of GATICs; (2) trace the origin of GATICs; and (3) decode the regulatory mechanism of GATICs. Furthermore, recent studies demonstrate the plasticity of GATIC and the interaction between GATIC and its surrounding factors (TIC niche or tumor microenvironment). All these investigations pave the way for the development of GATIC-targeted therapy, which is in the phase of preclinical studies and clinical trials. Here, we interpret the heterogeneity of GC from the perspectives of TIC by reviewing the above-mentioned fundamental and clinical studies of GATICs. Problems encountered during the GATIC investigations and the potential solutions are also discussed.
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影响因子：
10.6
作者：
Abdullah LN;Chow EK
通讯作者：
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影响因子：
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作者：
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DOI：
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作者：
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DOI：
10.1056/nejmoa1113205
发表时间：
2012-03-08
期刊：
The New England journal of medicine
影响因子：
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作者：
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