Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy.

Details

Serval ID
serval:BIB_C137742E6EEF
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy.
Journal
Cancer cell
Author(s)
Choi W., Porten S., Kim S., Willis D., Plimack E.R., Hoffman-Censits J., Roth B., Cheng T., Tran M., Lee I.L., Melquist J., Bondaruk J., Majewski T., Zhang S., Pretzsch S., Baggerly K., Siefker-Radtke A., Czerniak B., Dinney C.P., McConkey D.J.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Publication state
Published
Issued date
10/02/2014
Peer-reviewed
Oui
Volume
25
Number
2
Pages
152-165
Language
english
Notes
Publication types: Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Muscle-invasive bladder cancers (MIBCs) are biologically heterogeneous and have widely variable clinical outcomes and responses to conventional chemotherapy. We discovered three molecular subtypes of MIBC that resembled established molecular subtypes of breast cancer. Basal MIBCs shared biomarkers with basal breast cancers and were characterized by p63 activation, squamous differentiation, and more aggressive disease at presentation. Luminal MIBCs contained features of active PPARγ and estrogen receptor transcription and were enriched with activating FGFR3 mutations and potential FGFR inhibitor sensitivity. p53-like MIBCs were consistently resistant to neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy, and all chemoresistant tumors adopted a p53-like phenotype after therapy. Our observations have important implications for prognostication, the future clinical development of targeted agents, and disease management with conventional chemotherapy.
Keywords
Aged, Antineoplastic Combined Chemotherapy Protocols/therapeutic use, Biomarkers, Tumor/genetics, Blotting, Western, Carcinoma, Basal Cell/drug therapy, Carcinoma, Basal Cell/pathology, Carcinoma, Squamous Cell/drug therapy, Carcinoma, Squamous Cell/pathology, Cell Differentiation, Cell Proliferation, Cisplatin/administration & dosage, Clinical Trials, Phase II as Topic, Cohort Studies, Doxorubicin/administration & dosage, Drug Resistance, Neoplasm/genetics, Female, Gene Expression Profiling, Humans, Male, Methotrexate/administration & dosage, MicroRNAs/genetics, Muscle Neoplasms/classification, Muscle Neoplasms/drug therapy, Muscle Neoplasms/pathology, Mutation/genetics, Neoadjuvant Therapy, Neoplasm Invasiveness, Neoplasm Staging, PPAR gamma/genetics, PPAR gamma/metabolism, Prognosis, RNA, Messenger/genetics, Real-Time Polymerase Chain Reaction, Receptor, Fibroblast Growth Factor, Type 3/genetics, Receptor, Fibroblast Growth Factor, Type 3/metabolism, Receptors, Estrogen/genetics, Receptors, Estrogen/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Tumor Suppressor Protein p53/genetics, Urinary Bladder Neoplasms/classification, Urinary Bladder Neoplasms/drug therapy, Urinary Bladder Neoplasms/pathology, Vinblastine/administration & dosage
Pubmed
Web of science
Open Access
Yes
Create date
08/01/2021 15:34
Last modification date
09/01/2021 6:26
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