研究动态
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非小细胞肺癌预测生物标志物领域的快速变化。

The rapidly changing field of predictive biomarkers of non-small cell lung cancer.

发表日期:2024
作者: László József Tóth, Attila Mokánszki, Gábor Méhes
来源: Cell Death & Disease

摘要:

肺癌是全球男性和女性癌症相关死亡的主要原因,但美国和欧盟的死亡率最近随着吸烟率的逐渐下降而下降。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,出现了大量用于治疗转移性非小细胞肺癌 (NSCLC) 的靶向药物疗法。个性化肿瘤学旨在为患者精确匹配最有可能成功的治疗方法。人们进行了大量的研究来引入可以预测特定靶向治疗方法有效性的生物标志物。 EGFR 信号通路包括多个足以治疗人类癌症(包括非小细胞肺癌)的靶点。肺腺癌可能同时存在 EGFR 基因的激活突变和耐药突变,以及 KRAS 和 BRAF 癌基因的突变。不太常见但可靶向的基因改变包括 ALK、ROS1、RET 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变得显而易见。突变的积累通常会触发肿瘤特异性免疫防御,但免疫保护可能会作为一种攻击性特征而上调。免疫检查点的阻断可能导致肿瘤细胞杀伤的重新激活,并诱导各种肿瘤类型(例如肺癌)的显着肿瘤消退。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,因此需要对单个小活检或细胞学标本进行大量测试,这面临着样本数量和质量的重大问题的挑战。因此,生物标志物测试的有效性应由标准化政策和最佳材料使用来保证。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。版权所有 © 2024 Tóth、Mokánszki 和 Méhes。
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.Copyright © 2024 Tóth, Mokánszki and Méhes.