PDXNet Pilot Projects
The PDXNet Coordination Center organizes pilot projects with the goal of advancing research through collaborative projects between the Patient Trial and Development Centers. A list of projects by year follows.
Temozolomide Pilot Study
To determine the robustness of PDX studies, the PDXNet tested temozolomide drug response for three pre-validated PDX models (sensitive, resistant, and intermediate) across four blinded PDX Development and Trial Centers (PDTCs) using independently selected SOPs (bioRxiv)
Copy Number Variation Pilot Study
Large-scale DNA-based tracking of the evolution of copy number alterations during xenograft engraftment and passaging through the analysis of PDXNet SNParray, WES, and RNA-seq datasets in collaboration with the EuroPDX consortium, who have provided hundreds of WGS datasets.
Computational Assessment of PDX Models from PDXNet and PDMR
Specific aims include: (1) Perform systematic analysis of genetic alterations in existing PDX models, (2) Comparison of existing PDX models with TCGA pan cancer data, and (3) Matching existing PDMR and PDXnet models with ongoing NCI clinical trials
Identifying birinapant sensitive and resistant models and biomarkers of response
The goal of this pilot project will be two-fold: (1) to expand the number of PDX models tested with birinapant and with
matched dosing regimens, and (2) to identify clinically-suitable biomarkers that correlate with response and/or resistance to birinapant, in order to stratify patients most likely to benefit from treatment.
Studying novel combinational treatments for Renal Cell Carcinoma in PDX models and paired organoid
Will perform omics analyses, including single nucleus sequencing (sn-Seq), of original cancers, as well as PDX/organoid pairs before and after treatment to better understand the correlations among mutational profiles and responses to combinational therapy.
Targeting BRAF-mutant Colorectal Carcinomas with combination therapies
Our objective is to develop preclinical trials in PDX of Colorectal Carcinomas that provide a strong rationale for initiating clinical trials in patients.
Testing of high priority drug combinations across tumor types
The concept for a pilot would be for each PDTC to identify their highest priority drug combination which would then be tested in different tumor types with similar genetic profiles by the other PDTCs. Tests would also include the tumor type used by the originating PDTC for comparison. This provides independent confirmation of activity, potentially broadens applicability, and may increase the pool of PDXs for RNAseq studies of resistance pathways.