open access

Vol 10, No 6 (2014)
Case report
Published online: 2015-01-07
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Optimal treatment for metastatic bladder cancer

Estrella M. Carballido, Jonathan E. Rosenberg
Onkol. Prak. Klin 2014;10(6):347-356.

open access

Vol 10, No 6 (2014)
CASE REPORTS
Published online: 2015-01-07

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.

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.

Get Citation

Keywords

metastatic bladder cancer, urothelial carcinoma, immunotherapeutics, molecular markers, targeted therapies

About this article
Title

Optimal treatment for metastatic bladder cancer

Journal

Oncology in Clinical Practice

Issue

Vol 10, No 6 (2014)

Article type

Case report

Pages

347-356

Published online

2015-01-07

Bibliographic record

Onkol. Prak. Klin 2014;10(6):347-356.

Keywords

metastatic bladder cancer
urothelial carcinoma
immunotherapeutics
molecular markers
targeted therapies

Authors

Estrella M. Carballido
Jonathan E. Rosenberg

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