50IN - Genes, chromosomes and the treatment of bladder cancer

Date 29 September 2012
Event ESMO Congress 2012
Session Molecular answers and targets on the horizon for the treatment of GU malignancies
Topics Urothelial Cancers
Pathology/Molecular Biology
Presenter Jonathan Rosenberg
Authors J.E. Rosenberg
  • Memorial Sloan-Kettering Cancer Center, 10065 - New York, NY/US

Abstract

Molecular analysis of bladder cancer is transforming our understanding of this disease. The relative abundance of bladder tumor tissue from these patients due to frequent resections provides a major opportunity to understand the molecular pathogenesis. Non-muscle invasive bladder cancer tends to be characterized by oncogenic activation events (FGFR3 mutation, PIK3CA mutation), while muscle invasive bladder cancer is more associated with tumor suppressor gene inactivation (p53, Rb). DNA copy number analysis identifies multiple regions of recurrent chromosomal gains and losses, many of which delineate known oncogenes and tumor suppressor genes. High-throughput analysis of bladder cancer specimens is identifying multiple new targets that may be therapeutically tractable in subsets of patients, including Her2 overexpression and amplification, b-raf mutation, and TSC1 mutation. The clinical implications of the molecular events in bladder cancer have yet to be identified. Large-scale genomic efforts linking clinical data to outcome should lead to an improved understand of the molecular landscape of bladder cancer. Next-generation sequencing technologies are allowing the rapid assessment of molecular alterations, which may lead to clinical trials enriched for patients whose tumors contain druggable alterations. To capitalize on the genomic knowledge gained in bladder cancer, reliable molecular tests that are accepted by regulatory authorities, along with targeted agents aimed at actionable alterations are, need to break out of the current therapeutic stalemate. Trials targeting some of these novel alterations are beginning to enroll patients.

Disclosure

J.E. Rosenberg: 1. Imclone- research funding 2. Oncogenex- consulting 3. Boehringer-Ingelheim- consulting 4. GSK- research funding 5. Novartis- research funding