Abstract 5988: Intra-carotid artery brain metastasis models for evaluation of lung and breast cancer drugs

Abstract

Abstract Non-CNS metastatic brain cancer is about 10 times more common than CNS cancer. Lung cancer and breast cancer account for most brain metastasis. KRAS-mutant NSCLC compose a third lung adenocarcinoma, among which 17% to 55% will develop brain metastases. Likewise, more than a third HER2-positive breast cancer will develop brain metastasis. Among existing animal models, the ectopic injection in brain cannot reflect the mechanism of tumor invasion and metastasis, while tail vein and intra-cardiac injection usually produces extra-cerebral metastatic disease and the animals have to be sacrificed before brain metastases appeared. Here we developed several metastasis models injected by intra-carotid artery (ICA) to address these problems. Two KRAS-mutant lung cancer cells and two HER2-positive breast cancer cells selected by their metastasize potential were luciferase labeled for in vivo imaging and drug evaluation. The tumor pathology in brain was evaluated by H&E staining. Compared to ectopic models, these ICA models have natural dissemination and progression in the brain, which recapitulate the different pattern of metastatic lesions in the clinic. With synchronized growth rate and little variation compared to tail vein and intra-cardiac models, these tumor growth kinetics allow for more appropriate animal efficacy study. Both KRAS-sensitive and insensitive models have been developed and validated for the next generation drug development; HER-2 positive breast models with ICA method also showed a good discriminative power on anti-HER2 modalities including antibodies, small molecules and ADC. Meanwhile, ICA models with human immune cell reconstitution were also developed to support immune therapies in pre-clinical stage. In summary, we have developed a panel of intra-carotid artery brain metastatic models for drug evaluation, and demonstrated their superiority in growth kinetics, brain microenvironment, drug selectivity and immune component. These models can be a promising predictive tool for novel drug/modality discovery to target brain metastasis. Citation Format: Fuyang Wang, Yuying Yang, Haoxia Zhao, Chunlei Dai, Bingrui Han, Mengyao Zhang, Xia Xiong, Chao Zhang, Xuzhen Tang, Qunsheng Ji. Intra-carotid artery brain metastasis models for evaluation of lung and breast cancer drugs [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 5988.