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将分子生物学的临床研究转化为针对结直肠癌患者的个性化多学科治疗方法。

Translating clinical research of Molecular Biology into a personalized, multidisciplinary approach of colorectal cancer patients.

作者信息

Strambu V, Garofil D, Pop F, Radu P, Bratucu M, Popa F

机构信息

Department of General Surgery, "Carol Davila" Clinical Nephrology Hospital, Bucharest, Romania.

Department of Pathology, "Carol Davila" Clinical Nephrology Hospital, Bucharest, Romania.

出版信息

J Med Life. 2014 Mar 15;7(1):17-26. Epub 2014 Mar 25.

PMID:24653752
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3956090/
Abstract

Although multimodal treatment has brought important benefit, there is still great heterogeneity regarding the indication and response to chemotherapy in Stage II and III, and individual variations related to both overall survival and toxicity of new therapies in metastatic disease or tumor relapse. Recent research in molecular biology led to the development of a large scale of genetic biomarkers, but their clinical use is not concordant with the high expectations. The Aim of this review is to identify and discuss the molecular markers with proven clinical applicability as prognostic and/or predictive factors in CRC and also to establish a feasible algorithm of molecular testing, as routine practice, in the personalized, multidisciplinary approach of colorectal cancer patients in our country. Despite the revolution that occurred in the field of molecular marker research, only Serum CEA, Immunohistochemical analysis of mismatch repair proteins and PCR testing for KRAS and BRAF mutations have confirmed their clinical utility in the management of colorectal cancer. Their implementation in the current practice should partially resolve some of the controversies related to this heterogenic pathology, in matters of prognosis in different TNM stages, stage II patient risk stratification, diagnosis of hereditary CRC and likelihood of benefit from anti EGFR therapy in metastatic disease. The proposed algorithms of molecular testing are very useful but still imperfect and require further validation and constant optimization.

摘要

尽管多模式治疗带来了重要益处,但在II期和III期患者中,化疗的适应症和反应仍存在很大异质性,并且在转移性疾病或肿瘤复发中,新疗法的总生存期和毒性存在个体差异。分子生物学的最新研究促使大量基因生物标志物得以开发,但其临床应用并未达到人们的高度期望。本综述的目的是识别和讨论在结直肠癌中已被证明具有临床适用性的分子标志物,作为预后和/或预测因素,并在我国结直肠癌患者的个性化多学科治疗中,建立一种可行的分子检测算法作为常规做法。尽管分子标志物研究领域发生了变革,但只有血清癌胚抗原、错配修复蛋白的免疫组化分析以及KRAS和BRAF突变的PCR检测已证实其在结直肠癌治疗中的临床效用。将它们应用于当前实践应能部分解决与这种异质性病理相关的一些争议,包括不同TNM分期的预后、II期患者风险分层、遗传性结直肠癌的诊断以及转移性疾病中抗表皮生长因子受体治疗的获益可能性。所提出的分子检测算法非常有用,但仍不完善,需要进一步验证和持续优化。

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引用本文的文献

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Karyopherin α-2 is a reliable marker for identification of patients with high-risk stage II colorectal cancer.核转运蛋白α-2是识别高危II期结直肠癌患者的可靠标志物。
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本文引用的文献

1
Prognostic and predictive factors in colorectal cancer.结直肠癌的预后和预测因素。
Chirurgia (Bucur). 2012 Sep-Oct;107(5):555-63.
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Clinical and pathological tools for identifying microsatellite instability in colorectal cancer.用于识别结直肠癌微卫星不稳定性的临床和病理工具。
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Evolvement of the treatment paradigm for metastatic colon cancer. From chemotherapy to targeted therapy.转移性结直肠癌治疗模式的演变。从化疗到靶向治疗。
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Validation microsatellite path score in a population-based cohort of patients with colorectal cancer.验证基于人群的结直肠癌患者队列中的微卫星路径评分。
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Implementing prognostic and predictive biomarkers in CRC clinical trials.在 CRC 临床试验中实施预后和预测生物标志物。
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A combination of serum markers for the early detection of colorectal cancer.联合检测血清标志物用于结直肠癌的早期检测。
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9
Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer.错配修复缺陷作为氟尿嘧啶为基础的辅助治疗结肠癌无效的预测标志物。
J Clin Oncol. 2010 Jul 10;28(20):3219-26. doi: 10.1200/JCO.2009.27.1825. Epub 2010 May 24.
10
Prognostic and predictive biomarkers in resected colon cancer: current status and future perspectives for integrating genomics into biomarker discovery.切除的结肠癌中的预后和预测生物标志物:将基因组学纳入生物标志物发现中的现状和未来展望。
Oncologist. 2010;15(4):390-404. doi: 10.1634/theoncologist.2009-0233. Epub 2010 Mar 29.