PDXNet Community Engagement
PDXNet Network-Wide Submissions
The PDX Data Commons and Coordinating Center
Systematic establishment of robustness and standards in xenograft experiments and analysis
The PDX Data Commons and Coordinating Center (PDCCC) for PDXNet in Support of Preclinical Research
Large-scale DNA-based tracking of the evolution of copy number alterations during xenograft engraftment and
Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis (submitted, bioRxiv)
Conservation of copy number profiles during engraftment and passaging of patient derived cancer xenografts (In preparation)
Workshops and Trainings
UC Davis, Seven Bridges Cancer Genomics Cloud - an Ecosystem to Access and Analyze Petabytes of Cancer Data
PDX Trial and Development Center
CCNE1 Amplification Is Associated with Poor Prognosis in Patients with Triple Negative Breast Cancer. Zi-Ming Zhao, Susan E. Yost, Katherine E. Hutchinson, Sierra Min Li, Yate-Ching Yuan, Javad Noorbakhsh, Zheng Liu, Charles Warden, Xiwei Wu, Jeffrey Chuang, Yuan Yuan. BMC Cancer (2019) 19:96.
High-resolution deconstruction of evolution induced by chemotherapy treatments in breast cancer xenografts. Hyunsoo Kim, Pooja Kumar, Francesca Menghi, Javad Noorbakhsh, Eliza Cerveira, Mallory Ryan, Qihui Zhu, Guruprasad Ananda, Joshy George, Henry Chen, Susan Mockus, Chengsheng Zhang, Yan Yang, James Keck, R. Krishna Murthy Karuturi, Carol J Bult, Charles Lee, Edison T Liu, Jeffrey H Chuang. Scientific Reports 8: 17937 (2018).
Whole-exome sequencing capture kit biases yield false negative mutation calls in TCGA cohorts. Victor G. Wang, Hyunsoo Kim, Jeffrey H. Chuang. PLoS ONE 13(10): e0204912. (2018).
Systematic Establishment of Robustness and Standards in Patient-Derived Xenograft Experiments and Analysis. Evrard et al. (The PDXNet Consortium) (submitted).
Abstract: Patient-Derived Xenografts (PDXs) are tumor-in-mouse models for preclinical testing of cancer therapeutics. PDX collections, such as the NCI PDXNet, are developing into key resources for drug testing. However, variations in experimental and analysis procedures limit interpretability. To determine the robustness of PDX studies, the PDXNet tested temozolomide response for models from three patients in replicate across four PDX Development and Trial Centers (PDTCs) with all sites blinded. Prior experiments by the NCI Patient Derived Models Repository showed one was sensitive, one was resistant, and one was intermediate. Each PDTC used independent SOPs varying in establishment protocols, treatment scheduling, and response criteria. Every group independently and correctly identified the sensitive, resistant, and intermediate models. Moreover, growth assessments were concordant across all groups for five biostatistical measures. Next we benchmarked exome-seq and RNA-seq analysis pipelines on synthetic test sets. We then applied the best pipelines to xenograft replicates generated and sequenced by each PDTC, which yielded robust assessments across groups. These studies show that PDX drug responses and sequence results are reproducible across diverse protocols. We detail the range of procedures and analyses that yielded these consistent results. This includes cloud-based sharing of standardized software for PDX biostatistical assessments and sequence analysis.
DPYSL3 modulates mitosis, migration, and epithelial-to-mesenchymal transition in claudin-low breast cancer. Matsunuma R, Chan DW, Kim BJ, Singh P, Han A, Saltzman AB, Cheng C, Lei JT, Wang J, Roberto da Silva L, Sahin E, Leng M, Fan C, Perou CM, Malovannaya A, Ellis MJ. Proc Natl Acad Sci U S A 2018;115(51):E11978-E87.
Multimodal action of ONECUT2 in driving neuroendocrine prostate cancer. Kaochar S, Mitsiades N. Translational Cancer Research 2019:S198-S203. http://tcr.amegroups.com/article/view/27434
Proof-of-principle for inhibition of GATA2 in prostate cancer by a clinically available small molecule (submitted). Kaochar S, Rajapakshe K, Robertson M, Foley C, Fiskus W, Dong J, Huang S, Davis C, Ehli E, Coarfa C, Mitsiades N.
Protective autophagy elicited by RAF→MEK→ERK inhibition suggests a treatment strategy for RAS-driven cancers. Conan G. Kinsey1,2, Soledad A. Camolotto1, Amelie M. Boespflug1,3,4, Katrin P. Guillen1, Mona Foth 1, Amanda Truong1, Sophia S. Schuman1, Jill E. Shea5, Michael T. Seipp5, Jeffrey T. Yap1,6, Lance D. Burrell1, David H. Lum1, Jonathan R. Whisenant1,2, G. Weldon Gilcrease III1,2, Courtney C. Cavalieri1,7, Kaitrin M. Rehbein1, Stephanie L. Cutler1, Kajsa E. Affolter1,8, Alana L. Welm1,9, Bryan E. Welm1,5, Courtney L. Scaife1,5, Eric L. Snyder1,8 and Martin McMahon. Nat Med. 2019 Apr;25(4):620-627. doi: 10.1038/s41591-019-0367-9. Epub 2019 Mar 4
Targeting Resistance to Targeted Therapies: Combating a Resilient Foe. Devarakonda S, Govindan R. Clin Cancer Res. 2018 Dec 15;24(24):6112-6114. doi:10.1158/1078-0432.CCR-18-3178. Epub 2018 Oct 23. PubMed PMID: 30352903; PubMedCentral PMCID: PMC6295273.
Concurrent HER or PI3K Inhibition Potentiates the Antitumor Effect of the ERK Inhibitor Ulixertinib in Preclinical Pancreatic Cancer Models. Jiang H, Xu M, Li L, Grierson P, Dodhiawala P, Highkin M, Zhang D, Li Q, Wang-Gillam A, Lim KH. Mol Cancer Ther. 2018 Jul 31;PubMed PMID: 30065098.