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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisReviewForskningpeer review

DOI

  • Joshua J. Meeks, Northwestern University
  • ,
  • Hikmat Al-Ahmadie, Memorial Sloan-Kettering Cancer Center
  • ,
  • Bishoy M. Faltas, Cornell University
  • ,
  • John A. Taylor, University of Kansas Kansas City
  • ,
  • Thomas W. Flaig, University of Colorado Cancer Center
  • ,
  • David J. DeGraff, Pennsylvania State University
  • ,
  • Emil Christensen
  • Benjamin L. Woolbright, University of Kansas Kansas City
  • ,
  • David J. McConkey, Johns Hopkins University
  • ,
  • Lars Dyrskjøt

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.

OriginalsprogEngelsk
TidsskriftNature Reviews Urology
Vol/bind17
Nummer5
Sider (fra-til)259-270
Antal sider12
ISSN1759-4812
DOI
StatusUdgivet - maj 2020

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