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Induction of Invasive Transitional Cell Bladder Carcinoma in Immune Intact Human MUC1 Transgenic Mice: A Model for Immunotherapy Development
Published on: October 30, 2013
Systemic therapy in muscle-invasive and metastatic bladder cancer: current trends and future promises
Jeanny B Aragon-Ching1, Donald L Trump1
1Inova Schar Cancer Institute, Fairfax, VA, USA.
Abstract:
Bladder urothelial cancers remain an important urologic cancer with limited treatment options in the locally advanced and metastatic setting. While neoadjuvant chemotherapy for locally advanced muscle-invasive cancers has shown overall survival benefit, clinical uptake in practice have lagged behind. Controversies surrounding adjuvant chemotherapy use are also ongoing. Systemic therapies for metastatic bladder cancer have largely used platinum-based therapies without effective standard second-line therapy options for those who fail, although vinflunine is approved in Europe as a second-line therapy based on a Phase III trial, and most recently, atezolizumab, a checkpoint inhibitor, was approved by the US FDA. Given increasing recognition of mutational signatures expressed in urothelial carcinomas, several promising agents with use of VEGF-targeted therapies, HER2-directed agents and immunotherapies with PD-1/PD-L1 antibodies in various settings are discussed herein.
Insights
Bladder urothelial cancer treatments are limited, especially in advanced stages. Emerging therapies targeting mutations, VEGF, HER2, and immune checkpoints offer new hope for patients with metastatic bladder cancer.
Area of Science:
- Urologic Oncology
- Medical Oncology
- Cancer Genomics
Background:
- Bladder urothelial carcinoma presents limited therapeutic strategies for locally advanced and metastatic disease.
- Neoadjuvant chemotherapy shows survival benefits for muscle-invasive bladder cancer, but clinical adoption is slow.
- Platinum-based therapies are standard for metastatic bladder cancer, with limited effective second-line options.
Purpose of the Study:
- To review current treatment options for bladder urothelial cancers.
- To discuss emerging targeted therapies and immunotherapies for advanced bladder cancer.
- To highlight the role of mutational signatures in guiding treatment decisions.
Main Methods:
- Review of current literature on bladder cancer treatment.
- Discussion of clinical trial data for novel agents.
- Analysis of emerging therapeutic targets including VEGF, HER2, and PD-1/PD-L1 pathways.
Main Results:
- Limited efficacy of current standard therapies in advanced bladder cancer.
- Approval of atezolizumab as a recent advancement in immunotherapy for metastatic disease.
- Identification of promising targeted agents and immunotherapies based on mutational signatures.
Conclusions:
- There is a need for improved treatment options for advanced bladder cancer.
- Targeted therapies and immunotherapies show promise for overcoming limitations of current treatments.
- Understanding mutational signatures is crucial for developing personalized treatment strategies in urothelial carcinoma.
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