靶向治疗和免疫治疗的采用彻底改变了非小细胞肺癌的治疗格局。对于早期疾病，最近的研究证明了将靶向治疗和免疫治疗纳入治疗方案可以降低复发率。先进的基因组测序技术、对药物耐药机制的更好理解以及改进的药物设计推动了晚期肺癌的靶向治疗的发展。可靶向的分子改变的列表不断扩大，而下一代分子治疗已显示出绕过药物耐药的希望。肺癌患者可能通过免疫检查点抑制剂实现持久的疾病控制，然而大多数患者会发展免疫治疗耐药性。不同种类的耐药机制已被提出，包括T细胞活化受损、共抑制免疫检查点的存在以及免疫抑制性肿瘤微环境。正在开发的大量新型免疫治疗策略旨在针对这些耐药机制。本综述旨在简要概述非小细胞肺癌靶向治疗和免疫治疗的最新发展。我们于2022年6月使用PubMed搜索了关于非小细胞肺癌（NSCLC）靶向治疗和免疫治疗的所有原始论文和综述。搜索词包括“非小细胞肺癌”、“靶向治疗”、“免疫治疗”、“EGFR”、“ALK”、“ROS1”、“BRAF V600E”、“MET”、“RET”、“KRAS”、“HER2”、“ERBB2”、“NRG1”、“免疫检查点”、“PD-1”、“PD-L1”、“CTLA4”、“TIGIT”、“VEGF”、“癌疫苗”、“细胞治疗”、“肿瘤微环境”、“细胞因子”和“肠道菌群”。我们首先讨论了在早期非小细胞肺癌中纳入靶向治疗和免疫治疗的情况。这包括最新的临床数据，这些数据导致了新辅助免疫治疗、辅助靶向治疗和辅助免疫治疗在早期非小细胞肺癌的获得批准。第二部分专注于转移性非小细胞肺癌的靶向治疗。可靶向的改变的列表现在包括但不限于EGFR、ALK、ROS1、BRAF V600E、MET exon 14 skipping、RET、KRAS G12C、HER2和NRG1。还讨论了潜在的药物耐药机制和正在开发中的新型治疗方法。第三部分涵盖了转移性非小细胞肺癌中的免疫治疗，包括目前获得批准的免疫治疗（抗PD-(L)1和抗CTLA4），以及正在积极研究中的药物（如抗TIGIT、癌疫苗、细胞治疗、细胞因子和其他调节肿瘤微环境的试剂）。本综述涵盖了肺癌治疗中靶向治疗和免疫治疗的最新进展，并讨论了该领域的未来发展方向。2023 Annals of Translational Medicine.版权所有。

The adoption of targeted therapy and immunotherapy has revolutionised the treatment landscape of non-small cell lung cancer. For early staged disease, incorporation of targeted therapy and immunotherapy has recently been demonstrated to reduce recurrence. Development of targeted therapies in advanced lung cancer is driven by advanced genomic sequencing techniques, better understanding of drug resistance mechanisms, and improved drug designs. The list of targetable molecular alteration is continuously expanding, and next generation molecular therapies have shown promise in circumventing drug resistance. Lung cancer patients may achieve durable disease control with immune checkpoint inhibitors however most patients develop immunotherapy resistance. A wide spectrum of resistance mechanisms, ranging from impaired T-cell activation, presence of coinhibitory immune checkpoints, to immunosuppressive tumour microenvironment, have been proposed. A multitude of novel immunotherapy strategies are under development to target such resistance mechanisms. This review aims to provide a succinct overview in the latest development in targeted therapy and immunotherapy for NSCLC management.We searched all original papers and reviews on targeted therapy and immunotherapy in non-small cell lung cancer (NSCLC) using PubMed in June 2022. Search terms included "non-small cell lung cancer", "targeted therapy", "immunotherapy", "EGFR", "ALK", "ROS1", "BRAF V600E", "MET", "RET", "KRAS", "HER2", "ERBB2", "NRG1", "immune checkpoint", "PD-1", "PD-L1", "CTLA4", "TIGIT", "VEGF", "cancer vaccine", "cellular therapy", "tumour microenvironment", "cytokine", and "gut microbiota".We first discuss the incorporation of targeted therapy and immunotherapy in early staged NSCLC. This includes the latest clinical data that led to the approval of neoadjuvant immunotherapy, adjuvant immunotherapy and adjuvant targeted therapy for early staged NSCLC. The second section focuses on targeted therapy in metastatic NSCLC. The list of targetable alteration now includes but is not limited to EGFR, ALK, ROS1, BRAF V600E, MET exon 14 skipping, RET, KRAS G12C, HER2 and NRG1. Potential drug resistance mechanisms and novel therapeutics under development are also discussed. The third section on immunotherapy in metastatic NSCLC, covers immunotherapy that are currently approved [anti-PD-(L)1 and anti-CTLA4], and agents that are under active research (e.g., anti-TIGIT, cancer vaccine, cellular therapy, cytokine and other TME modulating agents).This review encompasses the latest updates in targeted therapy and immunotherapy in lung cancer management and discusses the future direction in the field.2023 Annals of Translational Medicine. All rights reserved.