Following a comprehensive molecular characterization of 412 muscle-invasive bladder cancers, researchers in The Cancer Genome Atlas (TCGA) Research Network have outlined five distinct expression subtypes, each of which may be targetable by different treatments.
One of the five subtypes might be particularly responsive to FGFR3 inhibitors, for example, while two other subtypes may be amenable to treatment with checkpoint inhibitors, TCGA investigators hypothesized on the basis of the analysis, which was recently published in Cell (2017; 171:540-56.e25).
“First and foremost, (the analysis) really elucidates a lot of biology about the heterogeneity of muscle-invasive bladder cancer, and then it suggests that these different subtypes may facilitate a more personalized medicine approach to treating patients with muscle-invasive disease,” said researcher Seth P. Lerner, MD, of Baylor College of Medicine, Houston.
The framework as published in Cell represents a refinement of the original report from TCGA investigators published in 2014 in Nature (2014; 507:315-22) that was based on analysis of just 131 bladder cancers.
One of the most significant updates is the identification of a mutation signature associated with favorable prognosis. In particular, an APOBEC-related mutational signature corresponded to a 75% 5-year survival, according to investigators.
“APOBEC-signature mutagenesis is associated with both a high mutation rate and improved clinical outcome, an expression subtype that we term ‘neuronal,’ ” the authors wrote in the more recent report.