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TMOD-24. DEVELOPMENT OF A NOVEL IN VIVO MODEL OF LUNG-TO-BRAIN METASTASIS PROGRESSION


 Brain metastases (BM) are the most common neoplasm to affect the adult central nervous system, occurring ten times more frequently than primary brain tumor. BM develop in 40–50% of advanced lung adenocarcinoma (LUAD), and the lack of durable response to chemotherapy, immunotherapy, or targeted therapy will result in death within a year of BM diagnosis. Despite the high burden of disease, dismal prognosis, and the increase in incidence over time, the biological underpinnings of BM remain poorly understood due to both the difficulty of obtaining a sizable collection of metastatic tissue samples as well as a lack of clinically relevant models. As such, it is possible that the inability to properly study this disease may result in metastasis driver-genes remaining undiscovered. Typical models of BM utilize direct implantation of tumor cells into the mouse brain, or inoculation into the blood via intracardiac/intracarotid injections; these routes are invasive and cannot fully recapitulate the entirety of the metastatic cascade. Here we present a novel, non-invasive method to develop primary lung tumors and brain metastases. A 10µL tumor cell suspension in phosphate-buffered saline was applied to the nostrils of lightly anesthetized mice, allowing direct deposit of cells into the lungs. Mice were monitored with bioluminescence imaging bi-weekly and culled at 2.5–3 months post-inoculation. Lungs and brains were also removed and imaged, where tumors in both organs were observed. Further research is necessary to elucidate either the linear or parallel progression of tumor formation within this model. Nonetheless, our technique presents a novel preclinical tool to interrogate the metastatic process, allowing validation of genetic drivers as well as therapeutic screening.