Moving towards Personalized Medicine in Muscle-Invasive Bladder Cancer: Where Are We Now and Where Are We Going?
Abstract
:1. Neoadjuvant Therapy in Muscle-Invasive Bladder Cancer (MIBC): An Overview
2. Predictive Biomarkers of Response to Cisplatin-Based Chemotherapy
3. Therapeutic Implications of BC Molecular Subtypes
4. Predictive Biomarkers of Immunotherapy Response
5. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Molecular Classification | Patients (n) | Subtypes | Histological and Molecular Characteristics | Ref. |
---|---|---|---|---|
Lund University | 308 BC | Urobasal A | High expression of FGFR3, CCND1, TP63, and KRT5 | [24] |
Urobasal B | ||||
Genomically unstable (GU) | Frequent TP53 mutations. CCNE and ERBB2 expression and low cytokeratin expression | |||
Squamous cell carcinoma-like (SCC) | High expression of basal keratins normally not expressed in the urothelium | |||
Infiltrated | Stromal and immune cell infiltration | |||
UNC | 262 High grade MIBC | Luminal | Expression of epithelial markers (E-cadherin/CDH1 and miR-200) and alterations in FGFR3 | [25] |
Basal | Sarcomatoid features. High expression of EGFR and its ligands | |||
MDA | 73 MIBC | Luminal | Features of active PPARγ and estrogen receptor transcription. FGFR3 mutations | [26] |
Basal | p63 activation and squamous differentiation | |||
p53-like | Presence of stromal markers and activation of p53 signature | |||
TCGA (2014) | 131 High grade MIBC | Cluster I | Luminal phenotype; presence of papillary tumors features | [7] |
Cluster II | Tumors with luminal phenotype but with a predominance of p53-like subtype features | |||
Cluster III | Correspond to basal subtype defined in the UNC and MD Anderson classifications | |||
Cluster IV | ||||
TCGA (2017) | 412 T2-4, N0-3, M0-1 MIBC | Luminal papillary (35%) | FOXA1, GATA3, and PPARG expression. FGFR3 alterations | [27] |
Luminal infiltrate (19%) | FOXA1, GATA3, and PPARG expression. Expression of EMT (high) and immune (moderate) markers | |||
Luminal (6%) | FOXA1, GATA3, and PPARG expression. High expression of KRT 20 | |||
Basal-SCC (35%) | High expression of immune response markers. CD44, KRT5, KRT6 and KRT14 expression. TP53 mutations | |||
Neuronal (5%) | High expression of neuroendocrine and neuronal markers | |||
BCMTG | 1750 MIBC transcriptomic profiles | Luminal papillary (24%) | Papillary morphology. Expression of FGFR3 and PPARG. Mutations in FGFR3 and KDM6A | [29] |
Luminal non-specified (8%) | Micropapillary morphology. PPARG expression. Mutations in ELF3 | |||
Luminal unstable (15%) | Expression of PPARG, E2F3, and ERBB2. Genomic instability. Mutation in TP53 and ERCC2 | |||
Stroma-rich (15%) | Stromal and immune cell (B cells) infiltration | |||
Basal/squamous (35%) | EGFR expression. Mutations in TP53 and RB1. Stromal and immune cell (CD8 T and NK cells) infiltration | |||
Neuroendocrine-like (3%) | Neuroendocrine differentiation. Loss of TP53 and RB1. Mutations in TP53 and RB1 |
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Pardo, J.C.; Ruiz de Porras, V.; Plaja, A.; Carrato, C.; Etxaniz, O.; Buisan, O.; Font, A. Moving towards Personalized Medicine in Muscle-Invasive Bladder Cancer: Where Are We Now and Where Are We Going? Int. J. Mol. Sci. 2020, 21, 6271. https://doi.org/10.3390/ijms21176271
Pardo JC, Ruiz de Porras V, Plaja A, Carrato C, Etxaniz O, Buisan O, Font A. Moving towards Personalized Medicine in Muscle-Invasive Bladder Cancer: Where Are We Now and Where Are We Going? International Journal of Molecular Sciences. 2020; 21(17):6271. https://doi.org/10.3390/ijms21176271
Chicago/Turabian StylePardo, Juan Carlos, Vicenç Ruiz de Porras, Andrea Plaja, Cristina Carrato, Olatz Etxaniz, Oscar Buisan, and Albert Font. 2020. "Moving towards Personalized Medicine in Muscle-Invasive Bladder Cancer: Where Are We Now and Where Are We Going?" International Journal of Molecular Sciences 21, no. 17: 6271. https://doi.org/10.3390/ijms21176271