Laboratory of Translational Oncology, School of Medicine, University of Crete, Heraklion, Greece.
Department of Medical Oncology, University General Hospital, Heraklion, Greece.
Expert Rev Mol Diagn. 2020 Mar;20(3):335-344. doi: 10.1080/14737159.2020.1724785. Epub 2020 Feb 3.
: The landscape of systemic treatment options for lung cancer has rapidly evolved with the emergence of immunomodulatory agents such as neutralizing antibodies targeting the programmed cell death protein 1 (PD-1) and its ligand (PD-L1). Another major breakthrough was the introduction of biomarkers, such as PD-L1 expression and tumor mutational burden (TMB), predicting response to immunotherapy. However, markers for monitoring treatment response are still lacking.: PD-L1 and TMB represent static pre-treatment evaluations. Dynamic biomarkers are required, along with static ones, to accurately predict and monitor immunotherapy response and to discriminate between responders and non-responders early in the course of treatment. The tumor immune contexture offers potential candidates that can be tested through the liquid biopsy approach, such as circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), exosomes, microRNAs (miRNAs), circular RNAs (circRNAs), RNA splice variants, and immune cell subsets.: A holistic approach combining information from tissue at the time of diagnosis and serial liquid biopsy data could lead to a novel combinatorial biomarker panel with enhanced treatment monitoring potential. Incorporating information from additional parts of the tumor-host ecosystem, such as metabolic markers and the microbiome is expected to provide added value to this strategy.
: 肺癌系统治疗方案的格局随着免疫调节剂的出现而迅速发展,如针对程序性细胞死亡蛋白 1 (PD-1)及其配体 (PD-L1)的中和抗体。另一个重大突破是引入了生物标志物,如 PD-L1 表达和肿瘤突变负担 (TMB),预测对免疫治疗的反应。然而,用于监测治疗反应的标志物仍缺乏。: PD-L1 和 TMB 代表治疗前的静态评估。需要动态生物标志物与静态生物标志物相结合,以准确预测和监测免疫治疗反应,并在治疗早期区分应答者和无应答者。肿瘤免疫微环境提供了潜在的候选标志物,可以通过液体活检方法进行测试,如循环肿瘤细胞 (CTC)、循环肿瘤 DNA (ctDNA)、外泌体、微小 RNA (miRNA)、环状 RNA (circRNA)、RNA 剪接变体和免疫细胞亚群。: 一种将诊断时组织信息与连续液体活检数据相结合的整体方法,可能会产生一种具有增强治疗监测潜力的新型组合生物标志物。纳入肿瘤-宿主生态系统其他部分的信息,如代谢标志物和微生物组,预计将为该策略提供附加值。