Levy Benjamin, Hu Zishuo I, Cordova Kristen N, Close Sandra, Lee Karen, Becker Daniel
Icahn School of Medicine, Mount Sinai Health System, New York, New York, USA
Icahn School of Medicine, Mount Sinai Health System, New York, New York, USA.
Oncologist. 2016 Sep;21(9):1121-30. doi: 10.1634/theoncologist.2016-0082. Epub 2016 Jul 7.
: A firmer understanding of the genomic landscape of lung cancer has recently led to targeted, therapeutic advances in non-small cell lung cancer. Historically, the reference standard for the diagnosis and genetic interrogation for advanced-stage patients has been tissue acquisition via computed tomography-guided core or fine needle aspiration biopsy. However, this process can frequently put the patient at risk and remains complicated by sample availability and tumor heterogeneity. In addition, the time required to complete the diagnostic assays can negatively affect clinical care. Technological advances in recent years have led to the development of blood-based diagnostics or "liquid biopsies" with great potential to quickly diagnose and genotype lung cancer using a minimally invasive technique. Recent studies have suggested that molecular alterations identified in cell-free DNA (cfDNA) or circulating tumor DNA can serve as an accurate molecular proxy of tumor biology and reliably predict the response to tyrosine kinase therapy. In addition, several trials have demonstrated the high accuracy of microRNA (miRNA) platforms in discerning cancerous versus benign nodules in high-risk, screened patients. Despite the promise of these platforms, issues remain, including varying sensitivities and specificities between competing platforms and a lack of standardization of techniques and downstream processing. In the present report, the clinical applications of liquid biopsy technologies, including circulating tumor cells, proteomics, miRNA, and cfDNA for NSCLC, are reviewed and insight is provided into the diagnostic and therapeutic implications and challenges of these platforms.
Although tumor biopsies remain the reference standard for the diagnosis and genotyping of non-small cell lung cancer, they remain fraught with logistical complexities that can delay treatment decisions and affect clinical care. Liquid diagnostic platforms, including cell-free DNA, proteomic signatures, RNA (mRNA and microRNA), and circulating tumor cells, have the potential to overcome many of these barriers, including rapid and accurate identification of de novo and resistant genetic alterations, real-time monitoring of treatment responses, prognosis of outcomes, and identification of minimal residual disease. The present report provides insights into new liquid diagnostic platforms in non-small cell lung cancer and discusses the promise and challenges of their current and future clinical use.
对肺癌基因组格局的更深入理解最近推动了非小细胞肺癌靶向治疗的进展。从历史上看，晚期患者诊断和基因检测的参考标准一直是通过计算机断层扫描引导的芯针活检或细针穿刺活检获取组织。然而，这个过程常常使患者面临风险，并且样本可用性和肿瘤异质性仍然使其复杂化。此外，完成诊断检测所需的时间可能会对临床护理产生负面影响。近年来的技术进步导致了基于血液的诊断方法或“液体活检”的发展，这种方法极有可能通过微创技术快速诊断肺癌并进行基因分型。最近的研究表明，在游离DNA（cfDNA）或循环肿瘤DNA中鉴定出的分子改变可以作为肿瘤生物学的准确分子替代物，并可靠地预测对酪氨酸激酶治疗的反应。此外，多项试验已证明微小RNA（miRNA）平台在鉴别高危筛查患者的癌性与良性结节方面具有很高的准确性。尽管这些平台前景广阔，但问题仍然存在，包括竞争平台之间不同的敏感性和特异性，以及技术和下游处理缺乏标准化。在本报告中，回顾了液体活检技术（包括循环肿瘤细胞、蛋白质组学、miRNA和cfDNA）在非小细胞肺癌中的临床应用，并深入探讨了这些平台的诊断和治疗意义及挑战。
尽管肿瘤活检仍然是非小细胞肺癌诊断和基因分型的参考标准，但它们仍然充满后勤复杂性，可能会延迟治疗决策并影响临床护理。液体诊断平台，包括游离DNA、蛋白质组学特征、RNA（mRNA和微小RNA）和循环肿瘤细胞，有可能克服许多这些障碍，包括快速准确地识别新发和耐药基因改变、实时监测治疗反应、预后评估以及识别微小残留疾病。本报告深入探讨了非小细胞肺癌新的液体诊断平台，并讨论了其当前和未来临床应用的前景与挑战。
