这篇摘要中的语法总体上是正确的，但有一个部分的句子结构存在一个小问题。这是一个稍微修改过的版本，改进了语法和流程：ROS1 酪氨酸激酶抑制剂 (TKI) 对 ROS1 阳性非小细胞肺癌非常有效，但耐药性仍然是一个挑战。我们研究了各种 TKI 针对野生型和突变型 ROS1 的活性，重点关注新出现的 L2086F 抗性突变。使用 Ba/F3 和 NIH3T3 细胞模型、CRISPR/Cas9 编辑的同基因野生型和突变型患者来源的细胞系以及体内肿瘤生长研究，我们将 I 型 TKI（克唑替尼、entrectinib、taletrectinib、lorlatinib 和 repotrectinib）与 I 型 TKI 进行了比较II TKI（卡博替尼和 Merestinib）和 I 型 FLT3 抑制剂 gilteritinib。 ROS1 L2086F 突变激酶表现出对 I 型 TKI 的抗性，而 II 型 TKI 保留了活性。 Gilteritinib 可抑制野生型和 L2086F 突变型 ROS1，但对 G2032R 突变无效。结构分析揭示了卡博替尼和吉尔特替尼的不同结合姿势，解释了它们对 L2086F 的功效。临床案例证明卡博替尼对 TKI 耐药、ROS1 L2086F 突变 NSCLC 患者有效。这项研究提供了 ROS1 L2086F 在新一代 TKI（包括大环抑制剂）背景下的第一份综合报告。虽然卡博替尼可有效抑制 ROS1 L2086F，但其多激酶抑制剂性质凸显了需要更具选择性和更好耐受性的 TKI 来克服激酶固有耐药性。 Gilteritinib 可能提供一种针对 ROS1 L2086F 的替代方案，具有明显的脱靶毒性，但需要进一步研究来充分评估其在这种情况下的潜力。© 2024。作者。

The grammar in this abstract is generally correct, but there's a minor issue with sentence structure in one part. Here's a slightly revised version with improved grammar and flow:ROS1 tyrosine kinase inhibitors (TKIs) are highly effective in ROS1-positive non-small cell lung cancer, but resistance remains a challenge. We investigated the activity of various TKIs against wildtype and mutant ROS1, focusing on the emerging L2086F resistance mutation. Using Ba/F3 and NIH3T3 cell models, CRISPR/Cas9-edited isogenic wildtype and mutant patient-derived cell lines, and in vivo tumor growth studies, we compared type I TKIs (crizotinib, entrectinib, taletrectinib, lorlatinib, and repotrectinib) to type II TKIs (cabozantinib and merestinib) and the type I FLT3 inhibitor gilteritinib. The ROS1 L2086F mutant kinase showed resistance to type I TKIs, while type II TKIs retained activity. Gilteritinib inhibited both wildtype and L2086F mutant ROS1 but was ineffective against the G2032R mutation. Structural analyses revealed distinct binding poses for cabozantinib and gilteritinib, explaining their efficacy against L2086F. Clinical cases demonstrated cabozantinib's effectiveness in patients with TKI-resistant, ROS1 L2086F mutant NSCLCs. This study provides the first comprehensive report of ROS1 L2086F in the context of later-generation TKIs, including macrocyclic inhibitors. While cabozantinib effectively inhibits ROS1 L2086F, its multi-kinase inhibitor nature highlights the need for more selective and better-tolerated TKIs to overcome kinase-intrinsic resistance. Gilteritinib may offer an alternative for targeting ROS1 L2086F with distinct off-target toxicities, but further studies are required to fully evaluate its potential in this setting.© 2024. The Author(s).