BackgroundSince the publication of the original work in 2014, significant progress has been made in the characterization of genomic alterations that drive oncogenic addiction of nonsmall cell lung cancer (NSCLC) and how the immune system can leverage non-oncogenic pathways to modulate therapeutic outcomes. This update evaluates and validates the recent and emerging data for prognostic and predictive biomarkers with therapeutic targets in NSCLC.Data sourcesWe performed a literature search from January 2015 to October 2023 using the keywords non-small cell lung cancer, clinical practice guidelines, gene mutations, genomic assay, immune cancer therapy, circulating tumor DNA, predictive and prognostic biomarkers, and targeted therapies.Study selection and data extractionWe identified, reviewed, and evaluated relevant clinical trials, meta-analyses, seminal articles, and published clinical practice guidelines in the English language.Data synthesisRegulatory-approved targeted therapies include those somatic gene alterations of EGFR (“classic” mutations, exon 20 insertion, and rare EGFR mutations), ALK, ROS1, BRAF V600, RET, MET, NTRK, HER2, and KRAS G12C. Data for immunotherapy and circulating tumor DNA in next-generation sequencing are considered emerging, whereas the predictive role for PIK3CA gene mutation is insufficient.ConclusionsAdvances in sequencing and other genomic technologies have led to identifying novel oncogenic drivers, novel resistance mechanisms, and co-occurring mutations that characterize NSCLC, creating further therapeutic opportunities. The benefits associated with immunotherapy in the perioperative setting hold initial promise, with their long-term results awaiting.

中文翻译：

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非小细胞肺癌治疗靶点的预后和预测生物标志物：2023 年最新进展、证据和建议

背景自 2014 年发表原创作品以来，在驱动非小细胞肺癌 (NSCLC) 致癌成瘾的基因组改变的表征以及免疫系统如何利用非致癌途径调节治疗结果方面取得了重大进展。本次更新评估和验证了 NSCLC 治疗靶点的预后和预测生物标志物的最新数据和新兴数据。数据源我们使用关键词非小细胞肺癌、临床实践指南、基因突变、2015 年 1 月至 2023 年 10 月进行了文献检索。基因组测定、免疫癌症治疗、循环肿瘤 DNA、预测和预后生物标志物以及靶向治疗。研究选择和数据提取我们确定、审查和评估了相关的临床试验、荟萃分析、开创性文章，并以英文出版了临床实践指南数据合成监管部门批准的靶向治疗包括 EGFR 的体细胞基因改变（“经典”突变、外显子 20 插入和罕见 EGFR 突变）、ALK、ROS1、BRAF V600、RET、MET、NTRK、HER2 和 KRAS G12C。下一代测序中的免疫治疗和循环肿瘤 DNA 数据被认为是新兴的，而 PIK3CA 基因突变的预测作用还不够。 结论 测序和其他基因组技术的进步已导致识别新的致癌驱动因素、新的耐药机制和同时发生的耐药机制。非小细胞肺癌的特征突变，创造了进一步的治疗机会。围手术期免疫治疗的相关益处具有初步前景，长期结果正在等待。