Clinical Biomarkers in Oncology Focus on Colorectal Cancer
Clinical Biomarkers in Oncology Focus on Colorectal Cancer
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DOI：
10.2165/01250444-200913020-00004
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发表时间：
2009-01-01
影响因子：
4
通讯作者：
Tejpar, Sabine
中科院分区：
文献类型：
--
作者：
De Roock, Wendy;Biesmans, Bart;Tejpar, Sabine
对结直肠癌分子生物学的快速了解使人们对分子标记的识别抱有很高的希望，这些标记将用于优化和量身定制的治疗方案。然而，许多已发表的关于基因特异性生物标志物的数据与他们的发现相互矛盾，目前还没有检测方法用于临床实践，除了在佐剂环境中的微卫星不稳定性(MSI)和鸟苷环化酶C(GCC)检测，在欧洲，KRAS突变检测被用于表皮生长因子受体(EGFR)靶向治疗转移疾病的环境中。最初的标记语假设驱动的方法失败的原因是多方面的。尽管有很好的生物学基础支持，但单一标记物，如肿瘤蛋白P53(TP53)基因突变，当应用于包含许多同步变化的复杂肿瘤类型时，在预测结果方面表现不佳。许多标记还存在技术缺陷，这是由于缺乏定量技术来捕捉分子变化的影响。从微阵列表达谱获得的标记的影响需要在基于更大的队列的研究中进一步研究，交叉验证研究将是必要的。最近，KRAS基因的突变被证明是转移性疾病对EGFR抑制剂反应的强烈负面预测因子。也有人提出，BRAF基因突变可能是EGFR抑制剂耐药性的预测因素，关于PIK3CA基因的作用，有一些相互矛盾的数据。需要进一步的研究，以帮助将最新的发现整合到个性化医疗的临床有用工具中。
Rapidly growing insight into the molecular biology of colorectal cancer has led to high hopes for the identification of molecular markers to be used in optimized and tailored treatment regimens. However, many of the published data on gene-specific biomarkers are contradictory in their findings, and no tests are currently used in clinical practice, with the exception of microsatellite instability (MSI) and guanylyl cyclase C (GCC) testing in the adjuvant setting, and in Europe KRAS mutation testing is used in the setting of epidermal growth factor receptor (EGFR)-targeted therapy for metastatic disease. There are many reasons for the failure of the initial marker hypothesis-driven approach. Although supported by a good biologic rationale, single markers such as tumor protein p53 (TP53) gene mutations, when applied to a complex tumor type containing many synchronous alterations, do not perform well in predicting outcome. Many markers also suffer from technical shortcomings, resulting from the lack of quantitative techniques to capture the impact of the molecular alteration. The impact of markers obtained from microarray expression profiling needs to be further investigated in studies based on much larger cohorts, and cross-validation studies will be essential.Recently, mutations in the KRAS gene were shown to be strong negative predictors of response to EGFR inhibitors in metastatic disease. It has also been suggested that BRAF gene mutations may be predictive of EGFR inhibitor resistance, and there are some conflicting data regarding the role of the PIK3CA gene. Further studies are needed to help integrate the latest findings into clinically useful tools for personalized medicine.