nvp-cgm097 and Lymphoma

More than 90% of drugs with preclinical activity fail in human trials, largely due to insufficient efficacy. We hypothesized that adequately powered trials of patient-derived xenografts (PDX) in mice could efficiently define therapeutic activity across heterogeneous tumors. To address this hypothesis, we established a large, publicly available repository of well-characterized leukemia and lymphoma PDXs that undergo orthotopic engraftment, called the Public Repository of Xenografts (PRoXe). PRoXe includes all de-identified information relevant to the primary specimens and the PDXs derived from them. Using this repository, we demonstrate that large studies of acute leukemia PDXs that mimic human randomized clinical trials can characterize drug efficacy and generate transcriptional, functional, and proteomic biomarkers in both treatment-naive and relapsed/refractory disease.

Topics: Animals; Antineoplastic Agents; Biomarkers, Tumor; Cell Lineage; Female; Gene Expression Profiling; Genes, p53; Heterografts; Humans; Internet; Isoquinolines; Leukemia; Leukemia, Experimental; Lymphoma; Male; Mice; Mice, Inbred NOD; Molecular Targeted Therapy; Neoplasm Proteins; Neoplasm Transplantation; Phenotype; Piperazines; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Proteome; Proto-Oncogene Proteins c-mdm2; Random Allocation; Randomized Controlled Trials as Topic; Research Design; Tissue Banks; Transcriptome; Xenograft Model Antitumor Assays