■肺癌是世界上最致命的恶性肿瘤。自从发现驱动基因以来,靶向治疗已被证明优于传统化疗,并彻底改变了非小细胞肺癌(NSCLC)的治疗前景.酪氨酸激酶抑制剂(TKIs)在表皮生长因子受体(EGFR)突变和间变性淋巴瘤激酶(ALK)融合患者中的显着成功已将治疗方法从基于铂的联合化疗转向靶向治疗。尽管基因融合在非小细胞肺癌中的发病率较低,对晚期难治性患者具有重要意义。然而,肺癌基因融合患者的临床特征和最新治疗进展还没有得到深入的探讨。本综述旨在总结非小细胞肺癌基因融合变异靶向治疗的最新研究进展,以提高临床医师的认识。
■我们搜索了PubMed数据库和美国临床肿瘤学会(ASCO),欧洲医学肿瘤学会(ESMO),和世界肺癌会议(WCLC)摘要2005年1月1日至2022年8月31日的会议记录,关键词为“非小细胞肺癌”,\"fusion\",\"重排\",“靶向治疗”和“酪氨酸激酶抑制剂”。
■我们全面列举了各种基因融合在非小细胞肺癌中的靶向治疗。ALK的融合,ROS原癌基因1(ROS1),和在转染过程中重排的原癌基因(RET)相对比其他基因更常见(NTRK融合,NRG1融合,FGFR融合,等。).在接受克唑替尼治疗的ALK重排NSCLC患者中,阿列替尼,布加替尼,或者是ensartinib,在一线治疗中,亚洲人群的疗效略好于非亚洲人群.揭示了色瑞替尼作为一线治疗在非亚洲ALK重排人群中可能具有略好的效果。在一线治疗中,克唑替尼在ROS1融合阳性NSCLC的亚洲人和非亚洲人中的效果可能相似。与亚洲人群相比,非亚洲人群更有可能使用selpercatinib和pralsetinib治疗RET重排的NSCLC。
■本报告总结了融合基因研究的现状和相关的治疗方法,以提高临床医生的理解,但是如何更好地克服耐药性仍然是一个需要探索的问题。
UNASSIGNED: Lung cancer is the most fatal malignant tumor in the world. Since the discovery of driver genes, targeted therapy has been demonstrated to be superior to traditional chemotherapy and has revolutionized the therapeutic landscape of non-small cell lung cancer (NSCLC). The remarkable success of tyrosine kinase inhibitors (TKIs) in patients with epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) fusions has shifted the treatment from platinum-based combination chemotherapy to targeted therapy. Although the incidence rate of gene fusion is low in NSCLC, it is of great significance in advanced refractory patients. However, the clinical characteristics and the latest treatment progress of patients with gene fusions in lung cancer have not been thoroughly explored. The objective of this narrative
review was to summarize the latest research progress of targeted therapy for gene fusion variants in NSCLC to improve understanding for clinicians.
UNASSIGNED: We conducted a search of PubMed database and American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), and World Conference on Lung Cancer (WCLC) abstracts meeting proceedings from 1 January 2005 to 31 August 2022 with the following keywords \"non-small cell lung cancer\", \"fusion\", \"rearrangement\", \"targeted therapy\" and \"tyrosine kinase inhibitor\".
UNASSIGNED: We comprehensively listed the targeted therapy of various gene fusions in NSCLC. Fusions of ALK, ROS proto-oncogene 1 (ROS1), and rearranged during transfection proto-oncogene (RET) are relatively more common than others (NTRK fusions, NRG1 fusions, FGFR fusions, etc.). Among ALK-rearranged NSCLC patients treated with crizotinib, alectinib, brigatinib, or ensartinib, the Asian population exhibited a slightly better effect than the non-Asian population in first-line therapy. It was revealed that ceritinib may have a slightly better effect in the non-Asian ALK-rearranged population as first-line therapy. The effect of crizotinib might be similar in Asians and non-Asians with ROS1-fusion-positive NSCLC in first-line therapy. The non-Asian population were shown to be more likely to be treated with selpercatinib and pralsetinib for RET-rearranged NSCLC than the Asian population.
UNASSIGNED: The present report summarizes the current state of fusion gene research and the associated therapeutic methods to improve understanding for clinicians, but how to better overcome drug resistance remains a problem that needs to be explored.