The group at GCCRI will continue studies focused on identifying active agents and combinations using xenograft models of pediatric sarcoma and kidney tumors. We will complete ongoing studies, and start new studies as described below. In addition we plan to characterize 18 new sarcoma PDX models (exome seq and RNAseq), and complete characterization of 33 PDX models where we have exome sequence data from the TARGET initiative, but where we lack RNAseq data. This will greatly expand the number of available sarcoma models that can be used in the future PPP being developed by the FNIH.
Our aims for the 6 month extension are:
Specific Aims Proposed studies during the extension period. 1. Complete studies with Amgen 509 (ES-7, ES-3, EW-5). 2. Complete in vivo studies with ONC201. 3. Undertake screening for PPTC drugs/combinations. 4. Evaluate PLX-038A combined with vincristine in sarcoma and kidney models. 5. Evaluate Talazoparib + Radiation in CHLA258 cell in vitro and in vivo, then expand if justified 6. To characterize 33 models by RNAseq that were omitted from the ALS cohort. 7 To characterize 18 rhabdomyosarcoma and 5 Ewing sarcoma PDX models, not previously characterized. 8. Complete submission of manuscripts reporting PPTC results.
Studies to be undertaken will continue to identify novel new agents and drug combinations that are active in preclinical models of pediatric solid tumors. This group will focus on models of high-risk sarcoma and kidney cancers that have been molecularly characterized.
|Lowery, Caitlin D; Dowless, Michele; Renschler, Matthew et al. (2018) Broad spectrum activity of the checkpoint kinase 1 inhibitor prexasertib as a single agent or chemopotentiator across a range of preclinical pediatric tumor models. Clin Cancer Res :|
|Murphy, Brendan; Yin, Han; Maris, John M et al. (2016) Evaluation of Alternative In Vivo Drug Screening Methodology: A Single Mouse Analysis. Cancer Res 76:5798-5809|