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Optimal Treatment for Metastatic Bladder Cancer

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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.

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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

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

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Authors and Affiliations

  1. Division of Hematology and Medical Oncology, Mayo Clinic Cancer Center, 13400 E Shea Blvd, Scottsdale, AZ, 85259, USA

    Estrella M. Carballido

  2. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Jonathan E. Rosenberg

  3. Weill Cornell Medical College, New York, NY, 10065, USA

    Jonathan E. Rosenberg

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Carballido, E.M., Rosenberg, J.E. Optimal Treatment for Metastatic Bladder Cancer. Curr Oncol Rep 16, 404 (2014). https://doi.org/10.1007/s11912-014-0404-2

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