Bladder cancer organoids as a functional system to model different disease stages and therapy response. Academic Article uri icon

Overview

abstract

  • Bladder Cancer (BLCa) inter-patient heterogeneity is the primary cause of treatment failure, suggesting that patients could benefit from a more personalized treatment approach. Patient-derived organoids (PDOs) have been successfully used as a functional model for predicting drug response in different cancers. In our study, we establish PDO cultures from different BLCa stages and grades. PDOs preserve the histological and molecular heterogeneity of the parental tumors, including their multiclonal genetic landscapes, and consistently share key genetic alterations, mirroring tumor evolution in longitudinal sampling. Our drug screening pipeline is implemented using PDOs, testing standard-of-care and FDA-approved compounds for other tumors. Integrative analysis of drug response profiles with matched PDO genomic analysis is used to determine enrichment thresholds for candidate markers of therapy response and resistance. Finally, by assessing the clinical history of longitudinally sampled cases, we can determine whether the disease clonal evolution matched with drug response.

publication date

  • April 18, 2023

Research

keywords

  • Urinary Bladder Neoplasms

Identity

PubMed Central ID

  • PMC10113240

Scopus Document Identifier

  • 85152863535

Digital Object Identifier (DOI)

  • 10.1038/s41467-023-37696-2

PubMed ID

  • 37072390

Additional Document Info

volume

  • 14

issue

  • 1