Comprehensive Cancer Center der LMU - Krebszentrum München, München, Germany.
Cancer Treat Rev. 2013 Oct;39(6):592-601. doi: 10.1016/j.ctrv.2012.12.011. Epub 2013 Jan 31.
In metastatic colorectal cancer (mCRC), an improved understanding of the underlying pathology and molecular biology has successfully merged with advances in diagnostic techniques and local/systemic therapies as well as improvements in the functioning of multidisciplinary teams, to enable tailored treatment regimens and optimized outcomes. Indeed, as a result of these advancements, median survival for patients with mCRC is now in the range of 20-24months, having approximately tripled in the last 20years. The identification of KRAS as a negative predictive marker for activity of epidermal growth factor receptor (EGFR)-targeted monoclonal antibodies (mAbs), such as panitumumab (Amgen, Thousand Oaks, USA) and cetuximab (ImClone, Branchburg, USA), has perhaps had the greatest impact on patient management. This meant that, for the first time, mCRC patients unlikely to respond to a targeted therapy could be defined ahead of treatment. Ongoing controversies such as whether patients with KRAS G13D- (or BRAF V600-) mutated tumours can still respond to EGFR-targeted mAbs and the potential impact of inter- and intra-tumour heterogeneity on tumour sampling show that the usefulness of KRAS as a biomarker has not yet been exhausted, and that other downstream biomarkers should be considered. Conversely, a predictive biomarker for anti-angiogenic agents such as bevacizumab (Genentech, San Francisco, USA) in the mCRC setting is still lacking. In this review we will discuss the discovery and ongoing investigation into predictive biomarkers for mCRC as well as how recent advances have impacted on clinical practice and ultimately the overall cost of treatment for these patients.
在转移性结直肠癌（mCRC）中，对潜在病理学和分子生物学的深入了解与诊断技术的进步、局部/系统治疗的进步以及多学科团队功能的提高相结合，使我们能够制定个性化的治疗方案并优化治疗效果。事实上，由于这些进展，mCRC 患者的中位生存期现在达到 20-24 个月，在过去 20 年中大约增加了两倍。KRAS 的鉴定作为表皮生长因子受体（EGFR）靶向单克隆抗体（mAb）如 panitumumab（美国安进公司）和 cetuximab（美国 ImClone 公司）活性的阴性预测标志物，可能对患者管理产生了最大的影响。这意味着，首次可以在治疗前确定不太可能对靶向治疗有反应的 mCRC 患者。目前仍存在争议，例如 KRAS G13D-（或 BRAF V600-）突变肿瘤患者是否仍能对 EGFR 靶向 mAb 有反应，以及肿瘤采样中肿瘤内和肿瘤间异质性的潜在影响表明，KRAS 作为生物标志物的用途尚未耗尽，应考虑其他下游生物标志物。相反，mCRC 环境中抗血管生成药物如 bevacizumab（美国基因泰克公司）的预测性生物标志物仍然缺乏。在这篇综述中，我们将讨论 mCRC 预测性生物标志物的发现和正在进行的研究，以及最近的进展如何影响临床实践，并最终影响这些患者的总体治疗成本。
