Through collaboration with major disease groups in the Dana-Farber Cancer Institute, Brigham and Women's Hospital, and Boston Children Hospital Cancer Centers, we have made a large collection of patient derived models of brain tumors, hematologic tumors, and many other solid tumors available to academic and industrial researchers worldwide.
In collaboration with Dr Keith Ligon at DFCI, CPDM has generated a collection of 50+ orthotopic brain metastasis PDX models of diverse origins of primary cancers (lung, skin, breast, colon, esophagus, testis, and others), from the most common breast carcinoma, melanoma, and lung adenocarcinoma to the rare neuroendrocrine carcinoma, prostate adenocarcinoma, esophageal adenocarcinoma, yolk sac tumor, ovarian carcinoma, lymphoma, sarcoma, and small cell lung carcinoma. In addition, CPDM also has a large collection of primary brain cancer models (PDX and PDCL of spheroid/organoid/adherent cultures). These primary brain tumor models cover a wide range of diagnoses and include several rare glioma models. Researchers can select models by mutation/alteration of BRAFV600E, IDH1R132H, H3F3AK27M, H3F3AG35R, EGFRvIII, by MGMT promoter methylation status. The collection includes PDX models of glioblastoma, pineoblastoma, medulloblastoma, atypical teratoid rhabdoid tumor, and primitive neuroectodermal tumor. Many of these brain cancer models have matching PDX and PDCL models (spheroid/organoid or adherent cultures) from the same patients. These models have been used in many publications, including the recent Nature. 2020 .
CPDM also has over 300+ hematologic cancer PDX models of diverse subtypes, including acute lymphocytic leukemia, acute myeloid leukemia, mature B-cell neoplasms, mature T- and NK-cell neoplasms, and myelodysplastic syndrome. AML models with t(9; 11) MLLT3-MLL, recurrent mutations in FLT3 and NPM1, as well as B-ALL models with t(12; 21) TEL-AML1, t(9; 22) BCR-ABL1, t(v; 11q23) MLL rearranged, t(1; 19) E2A-PBX1 and others are part of this collection. These PDX models were first published in Cancer Cell. 2016 and subsequently appeared in many studies. This model collection was previously distributed under the Public Repository of Xenografts (PRoXe) by Dr David Weinstock. In addition, we have about ~400 solid tumor PDX models with clinical and genomic annotations contributed by Novartis via a model sharing collaboration between DFCI and Novartis. These Novartis PDX models were previously published in the landmark Nat Med. 2015 study of using PDX models in high-throughput screening to predict clinical trial drug response.
Many of the models developed in our lab have been sequenced, and they come with rich clinical annotations, including data on whether tumors allocated for model creation have been previously exposed to immunotherapy, targeted therapy, chemotherapy, or radiation therapy.
We have produced an extensive experimental resource of PDXs from primary and metastatic tumors, coupled with comprehensive clinical and molecular annotation including cancer panel targeted sequencing as well as methylation profiles and gene expression. Basic clinical and genomic data of these PDX as well as PDCL cancer models can be visualized via DFCI’s cBioPortal (CPDM Pan-Cancer Patient Derived Models, registration required). Please visit the CPDM website for additional details. We frequently announce information on the latest cancer models we have created or in development/characterization pipeline via our LinkedIn and Twitter accounts.