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与癌症炎症相关的生物学机制:肿瘤微环境相关生物标志物的发现及其在实体瘤中的临床应用。

Biological mechanisms linked to inflammation in cancer: Discovery of tumor microenvironment-related biomarkers and their clinical application in solid tumors.

机构信息

IRCCS Regina Elena National Cancer Institute, Rome, Italy.

出版信息

Int J Biol Markers. 2020 Feb;35(1_suppl):8-11. doi: 10.1177/1724600820906155.

Abstract

Our view of cancer biology radically shifted from a "cancer-cell-centric" vision to a view of cancer as an organ disease. The concept that genetic and/or epigenetic alterations, at the basis of cancerogenesis, are the main if not the exclusive drivers of cancer development and the principal targets of therapy, has now evolved to include the tumor microenvironment in which tumor cells can grow, proliferate, survive, and metastasize only within a favorable environment. The interplay between cancer cells and the non-cellular and cellular components of the tumor microenvironment plays a fundamental role in tumor development and evolution both at the primary site and at the level of metastasis. The shape of the tumor cells and tumor mass is the resultant of several contrasting forces either pro-tumoral or anti-tumoral which have at the level of the tumor microenvironment their battle field. This crucial role of tumor microenvironment composition in cancer progression also dictates whether immunotherapy with immune checkpoint inhibitor antibodies is going to be efficacious. Hence, tumor microenvironment deconvolution has become of great relevance in order to identify biomarkers predictive of efficacy of immunotherapy. In this short paper we will briefly review the relationship between inflammation and cancer, and will summarize in 10 short points the key concepts learned so far and the open challenges to be solved.

摘要

我们对癌症生物学的看法从“以癌细胞为中心”的观点发生了根本性转变,认为癌症是一种器官疾病。癌症发生的基础是遗传和/或表观遗传改变,这些改变是癌症发展的主要(如果不是唯一的)驱动因素,也是治疗的主要靶点,这一概念现在已经发展到包括肿瘤微环境,只有在有利的环境中,肿瘤细胞才能生长、增殖、存活和转移。癌细胞与肿瘤微环境中非细胞和细胞成分之间的相互作用在肿瘤的发生和发展中起着至关重要的作用,无论是在原发性肿瘤还是在转移水平上都是如此。肿瘤细胞和肿瘤块的形状是几种对抗性力量的结果,这些力量要么促进肿瘤生长,要么抑制肿瘤生长,而这些力量在肿瘤微环境中存在着斗争的战场。肿瘤微环境组成在癌症进展中的这种关键作用也决定了免疫检查点抑制剂抗体的免疫疗法是否有效。因此,肿瘤微环境的解析对于识别免疫疗法疗效的预测性生物标志物变得非常重要。在这篇简短的论文中,我们将简要回顾炎症与癌症之间的关系,并总结到目前为止学到的 10 个关键概念和有待解决的开放性挑战。

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