MODL-01. TRACTABLE PATIENT-DERIVED MODELS FOR PRECLINICAL THERAPEUTIC STUDIES OF CNS METASTASES

Abstract INTRODUCTION Brain metastases are the most common brain tumors and occur in 10-30% of cancer patients, whereas leptomeningeal disease (LMD) occurs approximately 5% adults with systemic malignancies. Tractable preclinical models that faithfully represent metastasis to recapitulate LMD needed improve our understanding biological basis CNS as well developing effective therapeutic strategies. Our goal this study was generate representative using two methods. METHODS We isolated tumor cells from CSF 16 patients cytologically proven (9 NSCLC, 1 melanoma, ovarian cancer, endometrial 4 breast cancer) implanted subcutaneously into flank immunocompromised mice. Cell lines were also generated PDX tissues. Models characterized by next-generation sequencing (NGS). a model kinase-driven sarcoma intracardiac (IC) injection human mesenchymal stem (HMSC) expressing SPECC1L::RET fusion (CRISPR-Cas9 gene editing). The (HMSC-RET) labeled luciferase construct allow non-invasive bioluminescence imaging. RESULTS established three (2 lung, ovarian) (19% success rate compared 33% for solid tumors) matched cell resulting Intracardiac HMSC-RET resulted establishing several peripheral organs brain. SUMMARY AND CONCLUSIONS have LMD. Translational studies where clinical suspicion undergo sampling, NGS/ctDNA analysis, modeling crucial improving metastatic compartment investigating novel treatment paradigms. Future will be focused on examining biochemical genetic nature these