TRLS-04. PRECLINICAL VALIDATION OF A NOVEL THERAPEUTIC STRATEGY FOR CHOROID PLEXUS CARCINOMA

Abstract Choroid plexus carcinoma is a very rare pediatric tumor located in the fourth and lateral ventricles of brain. It known to have severe clinical history significant side effects because intensive noxious chemotherapies. Due disease’s rarity scarcity biologically relevant substrates, advance new therapeutical techniques for this condition has been exceedingly constrained. A human patient-derived CPC cell line (CCHE-45, Children Cancer Hospital Egypt) was subjected high-throughput screen (HTS); 427 top hits were identified, highlighting critical molecular targets CPC. Additionally, combination with numerous different identified synergistic combinations that lead way brand-new therapies. Based on vitro efficiency, CNS penetrance ability feasible translational potential, two using DNA alkylating or topoisomerase inhibitors an ataxia telangiectasia mutated rad3 (ATR) inhibitor (topotecan/elimusertib melphalan/elimusertib respectively) validated vivo. Pharmacokinetic studies revealed greater via intra-arterial (IA) delivery compared intravenous (IV) delivery, as well increased combination. Transcriptome analysis used evaluate mechanisms effect; deregulation several carcinogenic pathways (e.g. MYC, mTOR, p53) activation vital biological processes repair, apoptosis, hypoxia, interferon gamma). In genetic mouse model, IA administration melphalan elimusertib significantly survival. To best our knowledge, work first cells identify prospective combinatorial treatments it highlights effectiveness treatment