Pulse Brain · Growing Health Evidence Index
Tier 3 — Observational / field trialPeer-reviewed

A Functional Genetic Screen Identifies the Phosphoinositide 3-kinase Pathway as a Determinant of Resistance to Fibroblast Growth Factor Receptor Inhibitors in FGFR Mutant Urothelial Cell Carcinoma

Liqin Wang, Tonći Šuštić, Rodrigo Leite de Oliveira, Cor Lieftink, Pasi Halonen, Marieke van de Ven, Roderick L. Beijersbergen, Michel M. van den Heuvel, René Bernards, Michiel S. van der Heijden

European Urology · 2017

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Summary

Wang et al. conducted a functional genetic screen in FGFR-mutant urothelial carcinoma cell lines to identify molecular mechanisms of resistance to FGFR inhibitor therapy. The work implicated the PI3K signalling pathway as a principal determinant of therapeutic resistance, as suggested by the title and publication venue. These findings may inform combination therapeutic strategies targeting both FGFR and PI3K pathways in resistant disease.

UK applicability

This is fundamental cancer cell biology research with potential relevance to UK oncology drug development and precision medicine strategies for urothelial cancer. However, the findings are cell-line derived and would require clinical validation before direct translation to NHS treatment protocols.

Key measures

Gene set enrichment analysis; pathway activation status; cell line sensitivity to FGFR inhibitors; genetic screen hits conferring resistance phenotype

Outcomes reported

The study identified phosphoinositide 3-kinase (PI3K) pathway activation as a key determinant of resistance to fibroblast growth factor receptor (FGFR) inhibitors in FGFR-mutant urothelial cancer cells. The research employed functional genetic screening to elucidate resistance mechanisms in cell culture models.

Theme
General food systems / other
Subject
Other / interdisciplinary
Study type
Research
Study design
Laboratory / in vitro functional genetic screen
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Laboratory / in vitro
DOI
10.1016/j.eururo.2017.01.021
Catalogue ID
BFmokjoc86-wjxxzv

Topic tags

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