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结直肠癌中的场癌化:新前沿还是明日黄花?

Field cancerisation in colorectal cancer: a new frontier or pastures past?

作者信息

Patel Abhilasha, Tripathi Gyanendra, Gopalakrishnan Kishore, Williams Nigel, Arasaradnam Ramesh P

机构信息

Abhilasha Patel, Nigel Williams, Department of Colorectal Surgery, University Hospitals of Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, United Kingdom.

出版信息

World J Gastroenterol. 2015 Apr 7;21(13):3763-72. doi: 10.3748/wjg.v21.i13.3763.

Abstract

Despite considerable advances in our understanding of cancer biology, early diagnosis of colorectal cancer remains elusive. Based on the adenoma-carcinoma sequence, cancer develops through the progressive accumulation of mutations in key genes that regulate cell growth. However, recent mathematical modelling suggests that some of these genetic events occur prior to the development of any discernible histological abnormality. Cells acquire pro-tumourigenic mutations that are not able to produce morphological change but predispose to cancer formation. These cells can grow to form large patches of mucosa from which a cancer arises. This process has been termed "field cancerisation". It has received little attention in the scientific literature until recently. Several studies have now demonstrated cellular, genetic and epigenetic alterations in the macroscopically normal mucosa of colorectal cancer patients. In some reports, these changes were effectively utilised to identify patients with a neoplastic lesion suggesting potential application in the clinical setting. In this article, we present the scientific evidence to support field cancerisation in colorectal cancer and discuss important limitations that require further investigation. Characterisation of the field defect is necessary to enable early diagnosis of colorectal cancer and identify molecular targets for chemoprevention. Field cancerisation offers a promising prospect for experimental cancer research and has potential to improve patient outcomes in the clinical setting.

摘要

尽管我们对癌症生物学的理解有了长足的进步,但结直肠癌的早期诊断仍然难以实现。基于腺瘤-癌序列,癌症是通过调节细胞生长的关键基因中突变的逐步积累而发展的。然而,最近的数学模型表明,其中一些基因事件发生在任何可辨别的组织学异常出现之前。细胞获得了促肿瘤发生的突变,这些突变不会产生形态学变化,但易引发癌症形成。这些细胞可以生长形成大片黏膜,癌症由此产生。这个过程被称为“场癌变”。直到最近,它在科学文献中才受到很少的关注。现在有几项研究已经证明了结直肠癌患者宏观上正常的黏膜存在细胞、基因和表观遗传改变。在一些报告中,这些变化被有效地用于识别有肿瘤性病变的患者,这表明其在临床环境中有潜在应用价值。在本文中,我们提供科学证据来支持结直肠癌中的场癌变,并讨论需要进一步研究的重要局限性。对场缺陷进行特征描述对于实现结直肠癌的早期诊断和确定化学预防的分子靶点是必要的。场癌变为实验性癌症研究提供了一个有前景的方向,并且有可能在临床环境中改善患者的预后。

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