MBRS-65. CHEMI-GENOMIC ANALYSIS OF PATIENT-DERIVED XENOGRAFTS TO IDENTIFY PERSONALIZED THERAPIES FOR MEDULLOBLASTOMA. Issue 2 (22nd June 2018)

• Record Type: Journal Article
• Authors: Rusert, Jessica M; Jensen, James; Brabetz, Sebastian; Garancher, Alexandra; Udaka, Yoko T; Esparza, Lourdes A; Milde, Till; Cho, Yoon-Jae; Li, Xiao-Nan; Olson, James M; Crawford, John R; Levy, Michael L; Kool, Marcel; Pfister, Stefan; Tamayo, Pablo; Mesirov, Jill; Wechsler-Reya, Robert
• Is Part Of: Neuro-oncology. Volume 20:Issue 2(2018)supplement 2
• Page Start: i142
• Page End: i142
• Publication Date: 2018-06-22
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noy059.509
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Medulloblastoma (MB) is the most common malignant pediatric brain tumor. Even with an intensive therapeutic regimen of surgery, radiation and chemotherapy, one-third of patients still succumb to their disease and survivors suffer devastating side effects from the therapy. Thus, more effective and less toxic therapies are desperately needed. Genomic analyses have identified four major subgroups of MB – WNT, SHH, Group 3 and Group 4 – that differ in terms of mutations, gene expression and patient outcomes. Despite this heterogeneity, all MB patients currently receive similar therapies. To identify novel therapies for each subgroup of MB, we have assembled a panel of patient-derived xenograft (PDX) lines established by orthotopic transplantation of tumor cells obtained from surgery. We used these PDXs to perform high-throughput drug screening, and integrated drug response data with mutational, transcriptional, and epigenetic profiles. These studies revealed significant heterogeneity in drug responses among MB patients, and identified the RNA synthesis inhibitor Actinomycin D as a potent inhibitor of Group 3 MB, the most aggressive form of the disease. Based on these studies, we hope to move away from a one-size-fits-all approach and begin to treat each patient with therapies that are likely to be more effective against their tumor.