i3S - Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal.
Cancer Res. 2018 Jan 1;78(1):7-14. doi: 10.1158/0008-5472.CAN-17-2084. Epub 2017 Dec 20.
KRAS is one of the most frequently mutated oncogenes in cancer, being a potent initiator of tumorigenesis, a strong inductor of malignancy, and a predictive biomarker of response to therapy. Despite the large investment to understand the effects of KRAS activation in cancer cells, pharmacologic targeting of KRAS or its downstream effectors has not yet been successful at the clinical level. Recent studies are now describing new mechanisms of KRAS-induced tumorigenesis by analyzing its effects on the components of the tumor microenvironment. These studies revealed that the activation of KRAS on cancer cells extends to the surrounding microenvironment, affecting the properties and functions of its constituents. Herein, we discuss the most emergent perspectives on the relationship between KRAS-mutant cancer cells and their microenvironment components. .
KRAS 是癌症中最常发生突变的致癌基因之一,是肿瘤发生的有力启动子、恶性肿瘤的强诱导剂,也是治疗反应的预测生物标志物。尽管投入了大量资金来了解 KRAS 在癌细胞中的激活作用,但在临床水平上,KRAS 或其下游效应物的药物靶向治疗尚未成功。最近的研究通过分析 KRAS 对肿瘤微环境成分的影响,描述了 KRAS 诱导肿瘤发生的新机制。这些研究表明,KRAS 在癌细胞上的激活延伸到周围的微环境,影响其组成成分的特性和功能。在此,我们讨论了关于 KRAS 突变型癌细胞与其微环境成分之间关系的最突出的观点。