Evidence map›Paper›PMID 26270481›Full record

Trial reportPloS one2015

Development and Characterization of Bladder Cancer Patient-Derived Xenografts for Molecularly Guided Targeted Therapy.

Chong-Xian Pan, Hongyong Zhang, Clifford G Tepper, Tzu-yin Lin, Ryan R Davis, James Keck, Paramita M Ghosh, Parkash Gill, Susan Airhart, Carol Bult and 3 more

Open access · goldAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
64citing papers in PubMed, 2 pooled it
8.9field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

64 citing papers in PubMed, 2 syntheses or guidelines pooled it, 86 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
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  5. Review
  6. Article
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  12. Review
  13. Bioprinted research models of urological malignancy.Exploration (Beijing, China) · 2024
    Review
  14. Article
  15. Article
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  17. Review
  18. DNMT3A/Cancers · 2022
    Article
  19. Article
  20. 3'-[Journal of translational medicine · 2022
    Article

4 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 4 institutions in 1 country.

Chong-Xian PanDepartment of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA, 95817, United States of America; Department of Urology, University of California Davis, Sacramento, CA, 95817, United States of America; VA Northern California Health Care System, Mather, CA, 95655, United States of America.
Hongyong ZhangDepartment of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA, 95817, United States of America.
Clifford G TepperDepartment of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, United States of America.
Tzu-yin LinDepartment of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA, 95817, United States of America.
Ryan R DavisDepartment of Pathology and Laboratory Medicine, University of California Davis, Sacramento, CA, 95817, United States of America.
James KeckThe Jackson Laboratory, Sacramento, CA, 95838, United States of America.
Paramita M GhoshDepartment of Urology, University of California Davis, Sacramento, CA, 95817, United States of America; VA Northern California Health Care System, Mather, CA, 95655, United States of America; Department of Biochemistry and Molecular Medicine, University of California Davis, Sacramento, CA, 95817, United States of America.
Parkash GillUniversity of Southern California, Los Angeles, CA, 90089, United States of America.
Susan AirhartThe Jackson Laboratory, Sacramento, CA, 95838, United States of America.
Carol BultThe Jackson Laboratory, Sacramento, CA, 95838, United States of America.
David R GandaraDepartment of Internal Medicine, Division of Hematology/Oncology, University of California Davis, Sacramento, CA, 95817, United States of America.
Edison LiuThe Jackson Laboratory, Sacramento, CA, 95838, United States of America.
Ralph W de Vere WhiteDepartment of Urology, University of California Davis, Sacramento, CA, 95817, United States of America.
University of California, Davis · USJackson Laboratory · USUniversity of Southern California · USVA Northern California Health Care System · US

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Charles G Wray · 1985 to 2026
$61.9M
Development of targeting nanotherapeutics against bladder cancerI01BX001784 · VA · VA NORTHERN CALIFORNIA HEALTH CARE SYS · PI PAN, CHONG-XIAN · 2014 to 2017
–
BLRD VA I01 BX001784NCI NIH HHS 2 P30 CA 0933730NCI NIH HHS P30 CA034196
6 · The paper itself

Abstract

backgroundThe overarching goal of this project is to establish a patient-derived bladder cancer xenograft (PDX) platform, annotated with deep sequencing and patient clinical information, to accelerate the development of new treatment options for bladder cancer patients. Herein, we describe the creation, initial characterization and use of the platform for this purpose. METHODS AND

findingsTwenty-two PDXs with annotated clinical information were established from uncultured unselected clinical bladder cancer specimens in immunodeficient NSG mice. The morphological fidelity was maintained in PDXs. Whole exome sequencing revealed that PDXs and parental patient cancers shared 92-97% of genetic aberrations, including multiple druggable targets. For drug repurposing, an EGFR/HER2 dual inhibitor lapatinib was effective in PDX BL0440 (progression-free survival or PFS of 25.4 days versus 18.4 days in the control, p = 0.007), but not in PDX BL0269 (12 days versus 13 days in the control, p = 0.16) although both expressed HER2. To screen for the most effective MTT, we evaluated three drugs (lapatinib, ponatinib, and BEZ235) matched with aberrations in PDX BL0269; but only a PIK3CA inhibitor BEZ235 was effective (p<0.0001). To study the mechanisms of secondary resistance, a fibroblast growth factor receptor 3 inhibitor BGJ398 prolonged PFS of PDX BL0293 from 9.5 days of the control to 18.5 days (p<0.0001), and serial biopsies revealed that the MAPK/ERK and PIK3CA-AKT pathways were activated upon resistance. Inhibition of these pathways significantly prolonged PFS from 12 day of the control to 22 days (p = 0.001). To screen for effective chemotherapeutic drugs, four of the first six PDXs were sensitive to the cisplatin/gemcitabine combination, and chemoresistance to one drug could be overcome by the other drug.

conclusionThe PDX models described here show good correlation with the patient at the genomic level and known patient response to treatment. This supports further evaluation of the PDXs for their ability to accurately predict a patient's response to new targeted and combination strategies for bladder cancer.

Indexed as

AnimalsFemaleHeterograftsHumansImidazolesLapatinibMaleMAP Kinase Signaling SystemMiceMice, NudeNeoplasm ProteinsNeoplasm TransplantationPyridazinesQuinazolinesQuinolinesUrinary Bladder NeoplasmsdactolisibImidazolesLapatinibNeoplasm ProteinsponatinibPyridazinesQuinazolinesQuinolines

Identifiers

PMID26270481
PMCPMC4535951
OpenAlexW2129909745

What OpenQuestion holds

Textmetadata
LicenceCC0
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.