Evidence map›Paper›PMID 32235944›Full record

ReviewNature reviews. Urology2020

Genomic heterogeneity in bladder cancer: challenges and possible solutions to improve outcomes.

Joshua J Meeks, Hikmat Al-Ahmadie, Bishoy M Faltas, John A Taylor, Thomas W Flaig, David J DeGraff, Emil Christensen, Benjamin L Woolbright, David J McConkey, Lars Dyrskjøt

Abstract readReview
In one paragraph

Review in Nature reviews. Urology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 133 papers.

0numbers the graph read from it
0cells of the map it votes in
133citing papers in PubMed
–field-weighted citation impact
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

133 citing papers in PubMed.

  1. Trial
  2. TP53 mutation-biased CD8British journal of cancer · 2026
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73 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Joshua J MeeksDepartments of Urology and Biochemistry, Molecular Genetics, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA. joshua.meeks@northwestern.edu.
Hikmat Al-AhmadieDepartment of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.ORCID 0000-0002-2938-6627
Bishoy M FaltasDepartment of Medicine and Department of Cell and Developmental biology, Weill-Cornell Medicine, New York, NY, USA.ORCID 0000-0002-6432-1693
John A TaylorDepartment of Urology, University of Kansas Medical Center, Kansas City, KS, USA.ORCID 0000-0002-1780-3788
Thomas W FlaigUniversity of Colorado Cancer Center, Aurora, CO, USA.
David J DeGraffDepartments of Pathology, Biochemistry & Molecular Biology and Surgery, Division of Urology, Pennsylvania State University, College of Medicine, Hershey, PA, USA.
Emil ChristensenDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark.ORCID 0000-0001-7201-3933
Benjamin L WoolbrightDepartment of Urology, University of Kansas Medical Center, Kansas City, KS, USA.
David J McConkeyJohns Hopkins Greenberg Bladder Cancer Institute, Brady Urological Institute, Johns Hopkins University, Baltimore, MD, USA.
Lars DyrskjøtDepartment of Molecular Medicine, Aarhus University Hospital, Aarhus N, Denmark.ORCID 0000-0001-7061-9851

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4M
Institutional Career Development CoreKL2TR002385 · NCATS · WEILL MEDICAL COLL OF CORNELL UNIV · PI YUAN-SHAN ZHU · 2017 to 2026
$13.3M
SPORE in Bladder CancerP50CA221745 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI BAJORIN, DEAN F. · 2018 to 2024
$11.8M
The Role of EZH2 in Non-Muscle Invasive Bladder CancerI01BX003692 · VA · JESSE BROWN VA MEDICAL CENTER · PI Joshua James Meeks · 2017 to 2026
–
BLRD VA I01 BX003692NCATS NIH HHS KL2 TR002385NCI NIH HHS P30 CA008748NCI NIH HHS P50 CA221745
6 · The paper itself

Abstract

Histological and molecular analyses of urothelial carcinoma often reveal intratumoural and intertumoural heterogeneity at the genomic, transcriptional and cellular levels. Despite the clonal initiation of the tumour, progression and metastasis often arise from subclones that can develop naturally or during therapy, resulting in molecular alterations with a heterogeneous distribution. Variant histologies in tumour tissues that have developed distinct morphological characteristics divergent from urothelial carcinoma are extreme examples of tumour heterogeneity. Ultimately, heterogeneity contributes to drug resistance and relapse after therapy, resulting in poor survival outcomes. Mutation profile differences between patients with muscle-invasive and metastatic urothelial cancer (interpatient heterogeneity) probably contribute to variability in response to chemotherapy and immunotherapy as first-line treatments. Heterogeneity can occur on multiple levels and averaging or normalizing these alterations is crucial for clinical trial and drug design to enable appropriate therapeutic targeting. Identification of the extent of heterogeneity might shape the choice of monotherapy or additional combination treatments to target different drivers and genetic events. Identification of the lethal tumour cell clones is required to improve survival of patients with urothelial carcinoma.

Indexed as

Genetic HeterogeneityGenomeCarcinoma, Transitional CellHumansTreatment OutcomeUrinary Bladder Neoplasms

Identifiers

PMID32235944
PMCPMC7968350

What OpenQuestion holds

Textmetadata
LicenceTDM
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.