Holdenrieder Stefan
a Institute of Clinical Chemistry and Clinical Pharmacology, University Hospital Bonn , Germany ;
b Institute of Laboratory Medicine, German Heart Center of the Technical University Munich , Germany.
Scand J Clin Lab Invest Suppl. 2016;245:S40-5. doi: 10.1080/00365513.2016.1208446.
Blood-based biomarkers are valuable diagnostic tools for the management of lung cancer patients. They support not only differential diagnosis and histological subtyping, but are also applied for estimation of prognosis, stratification for specific therapies, monitoring of therapy response, surveillance monitoring and early detection of residual or progressive disease. Early diagnosis of lung cancer in high risk populations (screening) is a promising future indication but poses high medical and economic challenges to marker performance. The five mostly used classical 'tumor markers' show characteristic profiles of sensitivity and specificity for non-small cell lung cancer (NSCLC) like cytokeratin 19-fragments (CYFRA 21-1), carcino-embryonic antigen (CEA) and squamous cancer cell antigen (SCCA) as well as for small cell lung cancer (SCLC) like progastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE). Combined use and pattern recognition approaches enable highly accurate diagnosis, subtyping and therapy monitoring. For the interpretation of serial measurements on an individual level, marker-specific algorithms have to be developed. So-called companion diagnostics identify druggable molecular changes in signaling pathways of tumor tissue that can be addressed by targeted therapies. New highly sensitive technologies enable the convenient and serial molecular characterization on circulating tumor DNA (ctDNA) in the blood, too. This approach is helpful when biopsies are not available and to overcome tumor molecular heterogeneity and plasticity. As only a portion of patients have such druggable molecular changes, future strategies will imply the combined use of classical and new ctDNA-based biomarkers to optimize the management of lung cancer patients during the course of disease.
血液生物标志物是肺癌患者管理中很有价值的诊断工具。它们不仅有助于鉴别诊断和组织学分型，还可用于预后评估、特定治疗的分层、治疗反应监测、随访监测以及残余或进展性疾病的早期检测。在高危人群中早期诊断肺癌（筛查）是一个有前景的未来应用方向，但对标志物性能提出了很高的医学和经济挑战。五种最常用的经典“肿瘤标志物”对非小细胞肺癌（NSCLC）显示出特征性的敏感性和特异性谱，如细胞角蛋白19片段（CYFRA 21-1）、癌胚抗原（CEA）和鳞状细胞癌抗原（SCCA），对小细胞肺癌（SCLC）如胃泌素释放肽前体（ProGRP）和神经元特异性烯醇化酶（NSE）也是如此。联合使用和模式识别方法可实现高度准确的诊断、分型和治疗监测。为了在个体水平上解释系列测量结果，必须开发标志物特异性算法。所谓的伴随诊断可识别肿瘤组织信号通路中可通过靶向治疗解决的可药物化分子变化。新的高灵敏度技术也能够对血液中的循环肿瘤DNA（ctDNA）进行便捷的系列分子特征分析。当无法进行活检时，这种方法很有帮助，并且可以克服肿瘤分子的异质性和可塑性。由于只有一部分患者有这种可药物化分子变化，未来的策略将意味着联合使用经典的和基于ctDNA的新生物标志物，以在疾病过程中优化肺癌患者的管理。
