Identification of distinct basal and luminal subtypes of muscle-invasive bladder cancer with different sensitivities to frontline chemotherapy
By W. Choi, S. Porten, Seungchan Kim, D. Willis, E. Plimack, J. Hoffman-Censits, B. Roth, T. Cheng, M. Tran, I-ling Lee and 10 more. Cancer Cell, 2014
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Summary Muscle-invasive bladder cancers (MIBCs) are biologically heterogeneous and have widely variable clinical outcomes and responses to conventional chemotherapy. We discovered 3 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 (ER) transcription and were enriched with activating FGFR3 mutations and potentially FGFR inhibitor sensitivity. p53-like MIBCs were consistently resistant to neoadjuvant MVAC 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.
View Paper: https://www.semanticscholar.org/paper/194ad4999e19d60daed551034219ca55e7ce9573
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Citations in the corpus
- Impact of Molecular Subtypes in Muscle-invasive Bladder Cancer on Predicting Response and Survival after Neoadjuvant Chemotherapy. (2017, methodology): “These highly proliferative basal tumors demonstrated a poor prognosis when treated with surgery alone [11], but their prognosis was dramatically improved in the NAC cohort.”
- Gender and Bladder Cancer: A Collaborative Review of Etiology, Biology, and Outcomes. (2016, background): “Emerging data on UCB molecular subtypes may provide a link between the impact of microorganisms and patient clinicopathologic outcomes, such as whether different local microenvironments give rise to gender-specific tumor subtypes [47].”
- A Consensus Molecular Classification of Muscle-invasive Bladder Cancer (2019, methodology): “While outcome was associated with the consensus class for NAC-free patients (Fig.”
- Comprehensive Molecular Characterization of Muscle-Invasive Bladder Cancer. (2017, neutral): “…tyrosine kinases ERBB2/3 and FGFR1/3; and the transcription factors FOXA1, FOXM1, GATA3/6, HIF1A, KLF4 and STAT3 and TP63 (Breyer et al., 2016; Choi et al., 2014a; Dadhania et al., 2016; DeGraff et al., 2013; Eriksson et al., 2015; Godoy et al., 2016; Jones et al., 2016; Kardos et al.,…”