Importance of ROS1 gene fusions in non-small cell lung cancer.

IF 4.6 Q1 ONCOLOGY 癌症耐药(英文) Pub Date : 2023-01-01 DOI:10.20517/cdr.2022.105
Meri Muminovic, Carlos Rodrigo Carracedo Uribe, Andres Alvarez-Pinzon, Khine Shan, Luis E Raez
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引用次数: 1

Abstract

Targeted therapy has become one of the standards of care for advanced lung cancer. More than 10 genetic aberrations have been discovered that are actionable and several tyrosine kinase inhibitors (TKIs) have been approved to target each of them. Among several genetic aberrations that are actionable in non-small cell lung cancer (NSCLC), ROS1 translocations also known as gene fusion proteins, are found in only 1%-2% of the patient population. ROS1 mutations can usually be detected using a combination of techniques such as immunohistochemistry (IHC), Fluorescence in-situ testing (FISH), polymerase chain reaction (PCR), and next-generation sequencing (NGS). However, RNA NGS and ctDNA NGS (liquid biopsies) also contribute to the diagnosis. There are currently numerous FDA-approved agents for these tumors, including crizotinib and entrectinib; however, there is in-vitro sensitivity data and clinical data documenting responses to ceritinib and lorlatinib. Clinical responses and survival rates with these agents are frequently among the best compared to other TKIs with genetic aberrations; however, intrinsic or extrinsic mechanisms of resistance may develop, necessitating research for alternative treatment modalities. To combat the mechanisms of resistance, novel agents such as repotrectenib, cabozantinib, talotrectinib, and others are being developed. In this article, we examine the literature pertaining to patients with ROS1 tumors, including epidemiology, clinical outcomes, resistance mechanisms, and treatment options.

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ROS1基因融合在非小细胞肺癌中的重要性。
靶向治疗已成为晚期肺癌治疗的标准之一。已经发现了10多种可治疗的遗传畸变,并且已经批准了几种酪氨酸激酶抑制剂(TKIs)来针对每种畸变。在非小细胞肺癌(NSCLC)中可操作的几种遗传畸变中,ROS1易位也称为基因融合蛋白,仅在1%-2%的患者群体中发现。ROS1突变通常可以通过免疫组织化学(IHC)、荧光原位检测(FISH)、聚合酶链反应(PCR)和下一代测序(NGS)等技术的组合来检测。然而,RNA NGS和ctDNA NGS(液体活检)也有助于诊断。目前有许多fda批准的药物用于治疗这些肿瘤,包括克唑替尼和恩替尼;然而,有体外敏感性数据和临床数据记录了对ceritinib和lorlatinib的反应。与其他具有遗传畸变的tki相比,这些药物的临床反应和生存率通常是最好的;然而,内在或外在的耐药机制可能会发展,需要研究替代治疗方式。为了对抗耐药机制,正在开发诸如repotrectenib、cabozantinib、talotrectinib等新型药物。在这篇文章中,我们研究了与ROS1肿瘤患者有关的文献,包括流行病学、临床结果、耐药机制和治疗方案。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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