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Current Oncology Reports

, 16:404 | Cite as

Optimal Treatment for Metastatic Bladder Cancer

  • Estrella M. Carballido
  • Jonathan E. Rosenberg
Invited Commentary

Abstract

Metastatic bladder cancer is a lethal disease. Cisplatin-based chemotherapy, including the combination regimens gemcitabine–cisplatin and methotrexate–vinblastine–doxorubicin–cisplatin, are the standard first-line therapies. Second-line therapies have modest activity and no significant improvement in patient outcomes. Agents targeting growth, survival, and proliferation pathways have been added to cytotoxic therapy with limited added benefit to date. Modulating host immune response to cancer-associated antigens appears promising, with multiple new therapeutic approaches being pursued. Next-generation sequencing of invasive urothelial carcinoma has provided insights into the biology of this disease and potential actionable targets. Alterations in the receptor tyrosine kinase/Ras pathway and the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathway represent potential therapeutic targets in advanced disease, and novel agents are in development. Recent data from the Cancer Genome Atlas Research Network bladder cancer cohort and other efforts suggest that mutations in chromatin-regulatory genes are very common in invasive bladder tumors, and are more frequent than in other studied tumors. The discovery of new genomic alterations challenges drug development to change the course of this disease.

Keywords

Metastatic bladder cancer Urothelial carcinoma Immunotherapeutics Molecular markers Targeted therapies 

Abbreviations

AKT

Protein kinase B

CTLA4

Cytotoxic T lymphocyte antigen 4

EGFR

Epidermal growth factor receptor

FGFR

Fibroblast growth factor receptor

GC

Gemcitabine and cisplatin

MIBC

Muscle-invasive bladder cancer

mTOR

Mammalian target of rapamycin

MVAC

Methotrexate, vinblastine, doxorubicin, and cisplatin

PI3K

Phosphatidylinositol 3-kinase

RTK

Receptor tyrosine kinase

TCGA

The Cancer Genome Atlas

UC

Urothelial carcinoma

VEGF

Vascular endothelial growth factor

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Estrella M. Carballido and Jonathan E. Rosenberg declare that they have no conflict of interest

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Estrella M. Carballido
    • 1
  • Jonathan E. Rosenberg
    • 2
    • 3
  1. 1.Division of Hematology and Medical OncologyMayo Clinic Cancer CenterScottsdaleUSA
  2. 2.Genitourinary Oncology Service, Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkUSA
  3. 3.Weill Cornell Medical CollegeNew YorkUSA

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