PDF(Pubmed)
Abstract：
Lung cancer is a leading cause of cancer-related death worldwide in both men and women, however mortality in the US and EU are recently declining in parallel with the gradual cut of smoking prevalence. Consequently, the relative frequency of adenocarcinoma increased while that of squamous and small cell carcinomas declined. During the last two decades a plethora of targeted drug therapies have appeared for the treatment of metastasizing non-small cell lung carcinomas (NSCLC). Personalized oncology aims to precisely match patients to treatments with the highest potential of success. Extensive research is done to introduce biomarkers which can predict the effectiveness of a specific targeted therapeutic approach. The EGFR signaling pathway includes several sufficient targets for the treatment of human cancers including NSCLC. Lung adenocarcinoma may harbor both activating and resistance mutations of the EGFR gene, and further, mutations of KRAS and BRAF oncogenes. Less frequent but targetable genetic alterations include ALK, ROS1, RET gene rearrangements, and various alterations of MET proto-oncogene. In addition, the importance of anti-tumor immunity and of tumor microenvironment has become evident recently. Accumulation of mutations generally trigger tumor specific immune defense, but immune protection may be upregulated as an aggressive feature. The blockade of immune checkpoints results in potential reactivation of tumor cell killing and induces significant tumor regression in various tumor types, such as lung carcinoma. Therapeutic responses to anti PD1-PD-L1 treatment may correlate with the expression of PD-L1 by tumor cells. Due to the wide range of diagnostic and predictive features in lung cancer a plenty of tests are required from a single small biopsy or cytology specimen, which is challenged by major issues of sample quantity and quality. Thus, the efficacy of biomarker testing should be warranted by standardized policy and optimal material usage. In this review we aim to discuss major targeted therapy-related biomarkers in NSCLC and testing possibilities comprehensively.
摘要：
肺癌是全球男性和女性癌症相关死亡的主要原因，然而，美国和欧盟的死亡率最近正在下降，同时吸烟率逐渐下降。因此,腺癌的相对频率增加，而鳞状细胞癌和小细胞癌的相对频率下降。在过去的二十年中，出现了过多的靶向药物疗法来治疗转移性非小细胞肺癌（NSCLC）。个性化肿瘤学旨在使患者与具有最高成功潜力的治疗方法精确匹配。进行了广泛的研究以引入可以预测特定靶向治疗方法的有效性的生物标志物。EGFR信号通路包括用于治疗人类癌症(包括NSCLC)的若干足够的靶标。肺腺癌可能同时存在EGFR基因的激活和抗性突变，进一步,KRAS和BRAF癌基因的突变。频率较低但可靶向的遗传改变包括ALK，ROS1RET基因重排,以及MET原癌基因的各种改变。此外,抗肿瘤免疫和肿瘤微环境的重要性最近已经变得明显。突变的积累通常会引发肿瘤特异性免疫防御，但是免疫保护可能会被上调为一种侵袭性特征。免疫检查点的阻断导致肿瘤细胞杀伤的潜在重新激活，并在各种肿瘤类型中诱导显著的肿瘤消退。如肺癌。抗PD1-PD-L1治疗的治疗反应可能与肿瘤细胞的PD-L1表达相关。由于肺癌的诊断和预测特征广泛，需要从单个小活检或细胞学标本中进行大量检查，这受到样品数量和质量等重大问题的挑战。因此，应通过标准化政策和最佳材料使用来保证生物标志物检测的有效性.在这篇综述中，我们旨在讨论NSCLC中主要的靶向治疗相关生物标志物，并全面测试可能性。
