SCI 5 May 2023

Pre-clinical modelling of ROS1+ non-small cell lung cancer

(Lung Cancer; IF:6.08)

M. Terrones, K. Op de Beeck, G. Van Camp, G. Vandeweyer, Pre-clinical modelling of ROS1+ non-small cell lung cancer, Lung Cancer (2023), doi: https://doi.org/10.1016/j.lungcan.2023.107192

CORRESPONDENCE TO: E-mail address: marc.terronesbernat@uantwerpen.be

Abstract 摘要 

ROS1+ NSCLC Non-small cell lung cancer (NSCLC) is a heterogeneous group of diseases which accounts for 80% of newly diagnosed lung cancers. In the previous decade, a new molecular subset of NSCLC patients (around 2%) harboring rearrangements of the c-ros oncogene 1 was defined. ROS1+ NSCLC is typically diagnosed in young, nonsmoker individuals presenting an adenocarcinoma histology. Patients can benefit from tyrosine kinase inhibitors (TKIs) such as crizotinib and entrectinib, compounds initially approved to treat ALK- , MET- or NTRK- rearranged malignancies respectively. Given the low prevalence of ROS1-rearranged tumors, the use of TKIs was authorized based on pre-clinical evidence using limited experimental models, followed by basket clinical trials. After initiating targeted therapy, disease relapse is reported in approximately 50% of cases as a result of the appearance of resistance mechanisms. The restricted availability of TKIs active against resistance events critically reduces the overall survival. In this review we discuss the pre-clinical ROS1+ NSCLC models developed up to date, highlighting their strengths and limitations with respect to the unmet clinical needs. By combining gene-editing tools and novel cell culture approaches, newly developed pre-clinical models will enhance the development of nextgeneration tyrosine kinase inhibitors that overcome resistant tumor cell subpopulations.

非小细胞肺癌(NSCLC)是一种异质性的疾病，占新诊断肺癌的80%。在过去十年中，定义了携带c-ros癌基因1重排的NSCLC患者的新分子亚群（约2%）。ROS1+ NSCLC通常发生在年轻、非吸烟者中，且病理多为腺癌。患者可以从酪氨酸激酶抑制剂(TKIs)中获益，如crizotinib 和entrectinib，这两种药物最初分别被批准用于治疗ALK、MET或NTRK重排的恶性肿瘤。鉴于ROS1重排肿瘤的患病率较低，基于有限实验模型的临床前证据，TKIs被授权使用，然后进行一系列临床试验。在开始靶向治疗后，由于耐药机制的出现，大约50%的病例报告疾病复发。对耐药事件有活性的TKI的限制性应用严重降低了总生存率。在这篇综述中，我们讨论了迄今为止开发的临床前ROS1+ NSCLC模型，强调了它们在临床需求方面的优势和局限性。通过结合基因编辑工具和新的细胞培养方法，新开发的临床前模型将促进下一代酪氨酸激酶抑制剂的开发，以应对耐药的肿瘤细胞亚群。

来源 | 健康界

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