Biological markers in lung cancer: A clinician's perspective
Biological markers in lung cancer: A clinician's perspective
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DOI：
10.3233/cbm-2009-0124
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发表时间：
2010-01-01
影响因子：
3.1
通讯作者：
Huber, Rudolph Maria
中科院分区：
文献类型：
--
作者：
Tufman, Amanda;Huber, Rudolph Maria
迫切需要生物标志物来改善肺部肿瘤的早期检测、诊断和治疗。在过去的几年里，各种有前途的生物标志物已经出现在肺癌领域。与晚期肺癌相关的不良预后已经导致尝试开发肺癌筛查程序。影像学和痰细胞学在肺癌筛查中的作用是许多讨论的焦点，并且正在努力寻找合适的血液、痰或呼出气生物标志物用于检测早期肺癌。关于诊断，免疫组织化学分析是显微组织学的一种相对完善的辅助手段，作为区分起源于肺的肿瘤与来自其他地方的转移瘤的一种手段。而且，特别是在非小细胞肺癌的情况下，肺肿瘤的精确组织学亚分类在抗肿瘤治疗的选择中变得具有临床相关性，这表明免疫组织化学标记物的作用增加且明确。非小细胞肺癌的早期诊断和早期治疗是肺癌早期诊断和早期治疗的基础。特别是，是否手术的决定取决于特定纵隔淋巴结组中是否存在肿瘤细胞。生物标志物的使用可以揭示显微镜下淋巴结转移，这将不会注意到单独使用传统的组织学，并可以提供有关脑转移瘤的存在的早期信息。此外，有证据表明，特定的遗传因素使肿瘤易于转移，这可能在未来的风险分层中发挥作用。化疗可能与显着的毒性有关，不幸的是，并不总是成功地减缓肺癌的进展。个体化治疗的概念取决于我们预测哪种肿瘤对哪种药物有反应的能力。许多生物标志物已被认为对化疗反应具有预测价值，包括对顺铂反应的ERCC-1、对紫杉烷反应的β-微管蛋白和对吉西他滨反应的RRM 1。随着对NSCLC中EGFR通路的了解不断加深，开发了一类旨在抑制该通路的药物，包括厄洛替尼、吉非替尼和西妥昔单抗。这些药物的疗效似乎与EGFR基因突变的存在相关。目前已被广泛接受的是，EGFR中的特定激活突变可预测NSCLC对吉非替尼和厄洛替尼的反应。EGFR抑制剂治疗失败似乎也与EGFR中的特定突变和EGFR途径中其他蛋白质的突变相关。血管生成对肿瘤生长的重要性已经引起了对抑制血管生成的药物的兴趣。血管内皮生长因子（VEGF）及其受体是一个非常重要的研究对象，一旦开始治疗，生物标志物在患者监测中起着重要的作用。CYFRA-21-1和CEA的血清水平以及血清核小体水平与肿瘤对治疗的反应相关。此外，循环肿瘤细胞的血清水平以及循环肿瘤DNA中特定突变的检测可能在未来具有临床用途。本文介绍了生物标志物在肺癌检测、诊断和治疗中的作用，并介绍了与新生物标志物开发相关的数据，这些新生物标志物正在成为管理这种困难疾病的工具。
Biological markers are urgently needed to improve the early detection, diagnosis and treatment of lung tumours. Over the past several years various promising biomarkers have emerged in the field of lung cancer. The poor prognosis associated with advanced lung cancer has resulted in attempts to develop lung cancer screening programs. The role of imaging and sputum cytology in lung cancer screening is the focus of much discussion, and efforts to find a suitable blood, sputum or exhaled breath biomarker for the detection of early lung cancer are ongoing.Regarding diagnosis, immunohistochemical profiling is a relatively well established adjunct to microscopic histology as a means of differentiating tumours originating in the lung from metastases from elsewhere. And, in particular in the case of non small cell lung cancer, a precise histological sub-classification of lung tumours is becoming clinically relevant in the choice of anti-tumour therapy, suggesting an increased and defined role for immunohistochemical markers. Molecular changes which correlate with the proposed subclassification of non-small cell lung cancer have also been identified.The treatment of lung cancer is dependant on the stage at the time of diagnosis. In particular, the decision whether or not to operate is dependant on the presence or absence of tumour cells in specific groups of mediastinal lymph nodes. The use of biomarkers can reveal microscopic lymph node metastases which would go unnoticed using conventional histology alone, and can provide early information about the presence of brain metastases. In addition, there is evidence that specific genetic factors predispose tumours to metastasis, which may have a role in the future risk-stratification of patients.Treatment with chemotherapy can be associated with significant toxicity, and is unfortunately not always successful in slowing the progression of lung cancer. The concept of individualized treatment depends on our ability to predict which tumours will respond to which medications. Numerous biomarkers have been suggested to have predictive value in response to chemotherapy, including ERCC-1 for response to cisplatin, beta-tubulin for response to taxanes, and RRM1 for response to gemcitabine. Increasing understanding of the EGFR pathway in NSCLC has led to the development of a class of medications aimed at inhibiting this pathway, including erlotinib, gefitinib and cetuximab. The efficacy of these medications seems to correlate with the presence of mutations in the EGFR gene. It has now been widely accepted that specific activating mutations in EGFR predicts the response of NSCLC to gefitinib and erlotinib. The failure of treatment with EGFR inhibitors also appears to correlate with both specific mutations in EGFR and with mutations in other proteins in the EGFR pathway. The importance of angiogenesis to tumour growth has led to interest in medications which inhibit angiogenesis. The vascular endothelial growth factor (VEGF) and its receptor are of particular interest.Once treatment has been initiated, biomarkers play an important role in patient monitoring. The serum levels of CYFRA-21-1 and CEA, as well serum nucleosome levels, correlate with the tumour's response to therapy. In addition, serum levels of circulating tumour cells, as well as the detection of specific mutations in circulating tumour DNA may be of clinical use in the future. This paper describes the current role of biomarkers in the detection, diagnosis and treatment of lung cancer, and presents data relating to the development of new biomarkers which are emerging as tools in the management of this difficult disease.