期刊
CANCER CELL
卷 25, 期 2, 页码 152-165出版社
CELL PRESS
DOI: 10.1016/j.ccr.2014.01.009
关键词
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资金
- Baker Foundation
- MD Anderson Bladder SPORE [P50 CA91846]
- MD Anderson CCSG [P30 016672]
- American Cancer Society [IRG-92-027-17]
- [R01 CA151489]
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 PPAR gamma 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.
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