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Development of candidate cancer treatments is a resource-intensive process, with the research community continuing to investigate options beyond static genomic characterization. Toward this goal, we have established the genomic landscapes of 536 patient-derived xenograft (PDX) models across 25 cancer types, together with mutation, copy number, fusion, transcriptomic profiles, and NCI-MATCH arms. Compared with human tumors, PDXs typically have higher purity and fit to investigate dynamic driver events and molecular properties via multiple time points from same case PDXs. Here, we report on dynamic genomic landscapes and pharmacogenomic associations, including associations between activating oncogenic events and drugs, correlations between whole-genome duplications and subclone events, and the potential PDX models for NCI-MATCH trials. Lastly, we provide a web portal having comprehensive pan-cancer PDX genomic profiles and source code to facilitate identification of more druggable events and further insights into PDXs' recapitulation of human tumors.
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http://dx.doi.org/10.1038/s41467-021-25177-3 | DOI Listing |
Gut
August 2024
Institute of Digestive Disease, Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, The Chinese University of Hong Kong, Hong Kong, China
Objective: Probiotic is known to confer health benefits to humans. Here, we aimed to investigate the role of in colorectal cancer (CRC).
Design: abundance was evaluated in patients with CRC (n=489) and healthy individuals (n=536).
J Thromb Haemost
November 2022
Division of Hematology, Duke University Medical Center, Durham, North Carolina, USA.
Background: Anti-platelet factor 4 (PF4)/heparin immune complexes that cause heparin-induced thrombocytopenia (HIT) activate complement via the classical pathway. Previous studies have shown that the alternative pathway of complement substantially amplifies the classical pathway of complement activation through the C3b feedback cycle.
Objectives: These studies sought to examine the contributions of the alternative pathway to complement activation by HIT antibodies.
Cancers (Basel)
April 2022
Division of Oncology, Department of Clinical Sciences Lund, Lund University, Medicon Village, Scheelevägen 2, 223 81 Lund, Sweden.
Bladder cancer is a common and highly heterogeneous malignancy with a relatively poor outcome. Patient-derived tumor organoid cultures have emerged as a preclinical model with improved biomimicity. However, the impact of the different methods being used in the composition and dynamics of the models remains unknown.
View Article and Find Full Text PDFCancer Lett
June 2022
Davidoff Center, Rabin Medical Center, Beilinson Campus, Petah Tikva, Israel; Felsenstein Medical Research Center, Petah Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address:
The efficacy/safety of combining palbociclib (a CDK4/6 inhibitor) and sunitinib (a multi-targeted receptor tyrosine kinase inhibitor) was evaluated, using patient-derived xenograft (PDX) models. Twenty-three PDX mice models were developed from patients with various solid tumors. The mice were randomized to 4 groups (5-6 mice in each): control/palbociclib (100 mg/kg)/sunitinib (50 mg/kg)/combination.
View Article and Find Full Text PDFCancer Lett
June 2022
Department of Pharmacology, Nanjing Medical University, Nanjing, 210029, Jiangsu, China. Electronic address:
Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression; however, how CAFs are induced remains elusive. Sulfonylurea receptor 1 (SUR1) is a tumor-enhancer in non-small cell lung carcinoma (NSCLC). Here, we probed the influence of SUR1-expressing cancer cells on CAFs.
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