Abstract 5989: Brain metastasis mouse models for the evaluation of multikine inhibitors on ROS1-fusion-positive lung cancer

Abstract

Abstract Lung cancer is the leading cause of cancer-related death worldwide. Nearly 80% of lung cancers are non-small cell lung cancer (NSCLC) and 60% of them are diagnosed at the metastatic stage. Brain metastases affect more than 20% of NSCLC patients with poor prognosis and disabling symptoms. However, few therapies have been approved for the treatment of lung cancer brain metastases. A panel of rapid, predictive and clinically-relevant animal models are urgently needed to study the biology of brain metastases and to identify effective therapeutic approaches.Considering both progression and treatment of lung cancer brain metastases will be limited by the blood-brain barrier (BBB), here we describe methods for efficient establishment of brain metastases mouse models via different injection route (intracranial, intracardiac or intracarotid), to identify a model that permits tumor cell growth in the unique brain microenvironment without compromising BBB. Meanwhile, we established a novel ROS1 positive patient-derived xenograft (PDX) model together with its PDC sub-line, in which the exon 2 of SDC4 was fused to the exon 32 of ROS1 (SDC4ex2-ROS1ex32). The cell has been transduced with firefly luciferase expression vector for in vivo imaging detection. Three ROS1 inhibitors were tested on these brain metastasis and subcutaneous models to compare their efficacies. In summary, we established brain metastases lung cancer PDX models as reliable platforms for interrogation of targets and kinetics related mechanism and for drug screening. The use of such techniques will increase our knowledge of the metastatic process and help identify new targets of cancer metastasis. Citation Format: Hui Qi, Xia Xiong, Huanhuan Liu, Yuying Yang, Chunlei Dai, Haoxia Zhao, Bingrui Han, Xuzhen Tang, Qunsheng Ji. Brain metastasis mouse models for the evaluation of multikine inhibitors on ROS1-fusion-positive lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5989.