AUTHOR=Cornelius Albert , Foley Jessica , Bond Jeffrey , Nagulapally Abhinav B. , Steinbrecher Julie , Hendricks William P. D. , Rich Maria , Yendrembam Sangeeta , Bergendahl Genevieve , Trent Jeffrey M. , Sholler Giselle S. 

TITLE=Molecular Guided Therapy Provides Sustained Clinical Response in Refractory Choroid Plexus Carcinoma

JOURNAL=Frontiers in Pharmacology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2017.00652

DOI=10.3389/fphar.2017.00652

ISSN=1663-9812

ABSTRACT=<p>Choroid plexus carcinomas (CPCs) are rare, aggressive pediatric brain tumors with no established curative therapy for relapsed disease, and poor survival rates. <italic>TP53</italic> Mutation or dysfunction correlates with poor or no survival outcome in CPCs. Here, we report the case of a 4 month-old female who presented with disseminated CPC. After initial response to tumor resection and adjuvant-chemotherapy, the tumor recurred and metastasized with no response to aggressive relapse therapy suggesting genetic predisposition. This patient was then enrolled to a Molecular Guided Therapy Clinical Trial. Genomic profiling of patient tumor and normal sample identified a <italic>TP53</italic> germline mutation with loss of heterozygosity, somatic mutations including <italic>IDH2</italic>, and aberrant activation of biological pathways. The mutations were not targetable for therapy. However, targeting the altered biological pathways (mTOR, PDGFRB, FGF2, HDAC) guided identification of possibly beneficial treatment with a combination of sirolimus, thalidomide, sunitinib, and vorinostat. This therapy led to 92% reduction in tumor size with no serious adverse events, excellent quality of life and long term survival.</p>