Beyond conventional chemotherapy: Emerging molecular targeted and immunotherapy strategies in urothelial carcinoma

Sadakatsu Ikeda; Donna E Hansel; Razelle Kurzrock

doi:10.1016/j.ctrv.2015.06.004

Beyond conventional chemotherapy: Emerging molecular targeted and immunotherapy strategies in urothelial carcinoma

Cancer Treat Rev. 2015 Sep;41(8):699-706. doi: 10.1016/j.ctrv.2015.06.004. Epub 2015 Jun 23.

Authors

Sadakatsu Ikeda¹, Donna E Hansel², Razelle Kurzrock³

Affiliations

¹ Department of Medicine, Division of Hematology/Oncology, and Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, CA, USA. Electronic address: saikeda@ucsd.edu.
² Department of Pathology, Division of Anatomic Pathology, University of California, San Diego, La Jolla, CA, USA.
³ Department of Medicine, Division of Hematology/Oncology, and Center for Personalized Cancer Therapy, UC San Diego Moores Cancer Center, La Jolla, CA, USA.

PMID: 26138514
DOI: 10.1016/j.ctrv.2015.06.004

Abstract

Advanced urothelial carcinoma is frequently lethal, and improvements in cytotoxic chemotherapy have plateaued. Recent technological advances allows for a comprehensive analysis of genomic alterations in a timely manner. The Cancer Genome Atlas (TCGA) study revealed that there are numerous genomic aberrations in muscle-invasive urothelial carcinoma, such as TP53, ARID1A, PIK3CA, ERCC2, FGFR3, and HER2. Molecular targeted therapies against similar genetic alterations are currently available for other malignancies, but their efficacy in urothelial carcinoma has not been established. This review describes the genomic landscape of malignant urothelial carcinomas, with an emphasis on the potential to prosecute these tumours by deploying novel targeted agents and immunotherapy in appropriately selected patient populations.

Keywords: Genetic aberrations; Immune therapy; Targeted therapy; Urothelial carcinoma.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Carcinoma, Transitional Cell* / drug therapy
Carcinoma, Transitional Cell* / genetics
Carcinoma, Transitional Cell* / pathology
DNA-Binding Proteins / genetics
Disease Management
Histone Demethylases / genetics
Humans
Immunotherapy* / methods
Immunotherapy* / trends
Molecular Targeted Therapy* / methods
Molecular Targeted Therapy* / trends
Mutation
Neoplasm Proteins / genetics
Nuclear Proteins / genetics
Therapies, Investigational
Transcription Factors / genetics
Urologic Neoplasms* / drug therapy
Urologic Neoplasms* / genetics
Urologic Neoplasms* / pathology

Substances

ARID1A protein, human
DNA-Binding Proteins
KMT2D protein, human
Neoplasm Proteins
Nuclear Proteins
Transcription Factors
Histone Demethylases
KDM6A protein, human