非小细胞肺癌的新生物标志物和药物靶点

Grace Dy
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引用次数: 0

摘要

尽管治疗取得了进步,但非小细胞肺癌(NSCLC)的预后仍然很差,特别是在涉及转移的晚期首次诊断时。非小细胞肺癌的分类可以通过确定遗传、分子和组织学亚型来辅助,这些亚型在治疗选择中是重要的生物标志物。大多数靶向治疗现在是晚期非小细胞肺癌患者的一线治疗选择。在这里,它们已被证明可以改善总生存期(OS)和无进展生存期(PFS)。这类治疗包括针对非小细胞肺癌的驱动突变,如EGFR和ALK基因,以及针对程序性死亡蛋白1或其配体(程序性死亡配体1 [PD-L1])的免疫检查点抑制剂。在抗体-药物偶联物(ADC)中,细胞毒性载荷与单克隆抗体(mAb)偶联,单克隆抗体将药物传递给表达相应靶抗原的肿瘤细胞。虽然美国食品和药物管理局(FDA)还没有专门批准用于非小细胞肺癌的adc,但一些药物已经显示出希望,并正在研究作为非小细胞肺癌的治疗方法。作为adc靶点的新兴生物标志物,在治疗非小细胞肺癌中具有潜在的相关性,包括CEACAM5、TROP2、HER2和c-MET基因的产物。在此,本访谈提供了生物标志物和靶向治疗的概述,并与美国纽约州布法罗市罗斯威尔公园综合癌症中心的Grace Dy讨论了它们潜在的临床应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel Biomarkers and Drug Targets in Non-Small Cell Lung Cancer
Despite therapeutic advances, the prognosis of non-small cell lung cancers (NSCLC) is still very poor, especially when first diagnosed at later stages involving metastases. NSCLC classification can be aided by identifying genetic, molecular, and histological subtypes that are important biomarkers in treatment selection. The majority of targeted therapies are now first-line treatment options for eligible patients with advanced stages of NSCLC. Here they have been shown to improve overall survival (OS) and progression free survival (PFS). Such treatments include those aimed at driver mutations in NSCLC, such as the genes for EGFR and ALK, and immune checkpoint inhibitors such as those targeting programmed death protein 1 or its ligand (programmed death ligand 1 [PD-L1]). In antibody-drug conjugates (ADC), cytotoxic payloads are conjugated to monoclonal antibodies (mAb) that deliver the drug to tumour cells expressing the corresponding target antigen. While there are still no ADCs specifically approved for NSCLC by the U.S. Food and Drugs Administration (FDA), several agents have shown promise and are being investigated as therapy in NSCLC. Emerging biomarkers as targets for ADCs with potential relevance in the treatment of NSCLC include products of the genes CEACAM5, TROP2, HER2, and c-MET. Herein, this interview provides an overview of biomarkers and targeted therapies, with a discussion with Grace Dy, Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA, on their potential clinical utility.
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