文章：

结直肠癌的遗传预后和预测标志物

Genetic prognostic and predictive markers in colorectal cancer

原文发布日期：2009-06-18

DOI: 10.1038/nrc2645

类型: Review Article

开放获取: 否

要点：

1. The most studied markers of colorectal cancer prognosis and response to therapy are somatic mutations in KRAS, adenomatous polyposis coli(APC) and TP53. With the exception of KRAS mutations and their association with clinical resistance to epidermal growth factor receptor (EGFR)-specific antibody therapy, there is no compelling evidence that these markers have a role in clinical decision making.
2. Chromosomal instability is associated with a worse prognosis, and microsatellite instability with a better prognosis.
3. Germline polymorphisms have been described in the metabolic pathways of chemotherapeutic agents used in colorectal cancer — for example, 5-fluorouracil (5-FU) and irinotecan — which correlate with the degree of toxicity.
4. High-throughput expression and genotyping arrays are starting to generate novel markers and gene signatures that may be of use in the management of colorectal cancer. At present, these are not sufficiently validated to be clinically useful.
5. Linking the collection of tissue and germline DNA to well-designed clinical trials will increase our understanding of the mechanisms of poor prognosis, and with it our capacity to identify novel biomarkers.

要点翻译：

1. 结直肠癌预后和治疗反应研究中最为广泛的生物标志物包括KRAS、腺瘤性息肉病（APC）和TP53的体细胞突变。除KRAS突变及其与表皮生长因子受体（EGFR）特异性抗体治疗临床耐药性的关联外，目前尚无确凿证据表明这些标志物可用于临床决策。
2. 染色体不稳定性与较差的预后相关，而微卫星不稳定性则预示更好的预后。
3. 研究已发现结直肠癌化疗药物代谢通路中的种系多态性（例如5-氟尿嘧啶和伊立替康），这些多态性与药物毒性程度相关。
4. 高通量表达和基因分型芯片技术正在催生新型标志物和基因特征谱，或可应用于结直肠癌的临床管理。但目前这些发现尚未经过充分验证，暂不具备临床适用性。
5. 将组织样本和种系DNA的收集与精心设计的临床试验相结合，将深化我们对不良预后机制的理解，并提升我们识别新型生物标志物的能力。

英文摘要：

Despite many studies of the likely survival outcome of individual patients with colorectal cancer, our knowledge of this subject remains poor. Until recently, we had virtually no understanding of individual responses to therapy, but the discovery of the KRAS mutation as a marker of probable failure of epidermal growth factor receptor (EGFR)-targeted therapy is a first step in the tailoring of treatment to the individual. With the application of molecular analyses, as well as the ability to perform high-throughput screens, there has been an explosive increase in the number of markers thought to be associated with prognosis and treatment outcome in this disease. In this Review, we attempt to summarize the sometimes confusing findings, and critically assess those markers already in the public domain.

摘要翻译： 

尽管已开展大量结直肠癌患者个体生存结局的研究，我们对此的认知仍然有限。直至近期，我们对个体治疗反应几乎一无所知；而KRAS突变的发现——作为表皮生长因子受体（EGFR）靶向治疗可能失败的标志——标志着向个体化治疗迈出的第一步。随着分子分析技术的应用以及高通量筛查能力的实现，与该疾病预后及治疗结局相关的潜在标志物数量呈爆炸性增长。本文综述试图梳理这些有时令人困惑的发现，并对已进入公共领域的标志物进行批判性评估。

原文链接：

Genetic prognostic and predictive markers in colorectal cancer