Genetic subtypes of invasive bladder cancer

Recently completed cancer genomics projects identified intrinsic subtypes in muscle-invasive bladder cancers. Here we will describe the studies that led to their discovery and review their biological and clinical properties.

Whole genome mRNA expression profiling and unsupervised hierarchical cluster analyses identified intrinsic basal and luminal subtypes in muscle-invasive bladder cancers that are similar to the ones found in breast cancer. Tumors within each subtype have distinct responses to conventional cisplatin-based combination chemotherapy, and they contain gene expression signatures and DNA alterations that may render them vulnerable to clinically available targeted therapies.

Like their breast cancer counterparts, basal bladder cancers are characterized by poor clinical outcomes in the absence of effective systemic therapy, but a large fraction of them do respond to neoadjuvant chemotherapy, suggesting that the tumors should be managed aggressively. On the contrary, tumors that belong to the 'p53-like' subtype tend to be chemoresistant, so patients with these tumors should probably be managed differently. It seems likely that prospective identification of tumor intrinsic subtype membership could complement the use of DNA-based biomarkers to identify the groups of patients who will benefit the most from chemotherapy and targeted agents.