Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer.
Colorectal Carcinoma: A General Overview and Future Perspectives in Colorectal Cancer.
复制标题
DOI：
10.3390/ijms18010197
复制
发表时间：
2017-01-19
影响因子：
5.6
通讯作者：
Rodriguez Yoldi MJ
中科院分区：
文献类型：
--
作者：
Mármol I;Sánchez-de-Diego C;Pradilla Dieste A;Cerrada E;Rodriguez Yoldi MJ
结直肠癌（CRC）是第三大常见癌症，也是癌症相关死亡的第四大常见原因。大肠癌多见于西方国家，发病率逐年上升。患结直肠癌的概率约为4%-5%，患结直肠癌的风险与个人特征或习惯有关，如年龄、慢性病史和生活方式。在这种情况下，肠道微生物群具有相关作用，生态失调的情况可以通过慢性炎症机制诱导结肠癌发生。负责这一多相过程的一些细菌包括梭杆菌属、脆弱拟杆菌和肠道致病性大肠杆菌。CRC是由靶向癌基因、肿瘤抑制基因和DNA修复机制相关基因的突变引起的。根据突变的来源，结直肠癌可分为散发性（70%）;遗传性（5%）和家族性（25%）。导致这种情况的致病机制可分为三种类型，即染色体不稳定性（CIN）、微卫星不稳定性（MSI）和CpG岛甲基化表型（CIMP）。在这些类型的CRC中，已报告常见突变、染色体变化和易位影响重要途径（WNT、MAPK/PI 3 K、TGF-β、TP 53）和突变;特别是，基因如c-MYC、KRAS、BRAF、PIK 3CA、PTEN、SMAD 2和SMAD 4可用作患者结果的预测标志物。除了基因突变之外，ncRNA（如lncRNA或miRNA）的改变也可以促进致癌过程的不同步骤，并且在用作生物标志物时具有预测价值。因此，正在开发不同的基因和mRNA组以改善预后和治疗选择。CRC的一线治疗选择遵循基于肿瘤相关特征的多模式方法，通常包括手术切除，然后联合抗血管内皮生长因子（VEGF）和表皮生长受体（EGFR）的单克隆抗体或蛋白的化疗。除了传统的化疗，替代疗法（如琼脂糖肿瘤大珠，抗炎药，益生菌和金基药物）目前正在研究，以提高治疗效果和减少副作用。
Colorectal cancer (CRC) is the third most common cancer and the fourth most common cause of cancer-related death. Most cases of CRC are detected in Western countries, with its incidence increasing year by year. The probability of suffering from colorectal cancer is about 4%–5% and the risk for developing CRC is associated with personal features or habits such as age, chronic disease history and lifestyle. In this context, the gut microbiota has a relevant role, and dysbiosis situations can induce colonic carcinogenesis through a chronic inflammation mechanism. Some of the bacteria responsible for this multiphase process include Fusobacterium spp, Bacteroides fragilis and enteropathogenic Escherichia coli. CRC is caused by mutations that target oncogenes, tumour suppressor genes and genes related to DNA repair mechanisms. Depending on the origin of the mutation, colorectal carcinomas can be classified as sporadic (70%); inherited (5%) and familial (25%). The pathogenic mechanisms leading to this situation can be included in three types, namely chromosomal instability (CIN), microsatellite instability (MSI) and CpG island methylator phenotype (CIMP). Within these types of CRC, common mutations, chromosomal changes and translocations have been reported to affect important pathways (WNT, MAPK/PI3K, TGF-β, TP53), and mutations; in particular, genes such as c-MYC, KRAS, BRAF, PIK3CA, PTEN, SMAD2 and SMAD4 can be used as predictive markers for patient outcome. In addition to gene mutations, alterations in ncRNAs, such as lncRNA or miRNA, can also contribute to different steps of the carcinogenesis process and have a predictive value when used as biomarkers. In consequence, different panels of genes and mRNA are being developed to improve prognosis and treatment selection. The choice of first-line treatment in CRC follows a multimodal approach based on tumour-related characteristics and usually comprises surgical resection followed by chemotherapy combined with monoclonal antibodies or proteins against vascular endothelial growth factor (VEGF) and epidermal growth receptor (EGFR). Besides traditional chemotherapy, alternative therapies (such as agarose tumour macrobeads, anti-inflammatory drugs, probiotics, and gold-based drugs) are currently being studied to increase treatment effectiveness and reduce side effects.