THE DISCOVERY of molecular signatures, common in a newly defined subtype of bladder cancer, that are similar to the signatures in certain types of breast cancer, has shed light on new possibilities in the treatment of advanced bladder cancer.
The classification of cancers has recently undergone significant changes, from using the patterns in cancerous cells and tissues to the molecules and genes which make up the tissues themselves. It is this shift that has allowed scientists to notice these molecular similarities in a recent study.
Prof William Kim and Dr Benjamin Vincent, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA, and colleagues found that a subtype of bladder cancer, which has progressed from the initial site of the urothelium and into the surrounding muscular layer, shares molecular signatures with a subset of triple-negative breast cancers. The tumours found in this type of bladder cancer express low levels of the protein claudin in a similar manner to the tumours in these breast cancers.
Although this characteristic of breast cancer was already known, this is the first time it has been identified in tumours of bladder cancers.
In order to assess the molecular similarity between the two cancers, the team searched datasets in The Cancer Genome Atlas using gene signatures that define claudin-low tumours in breast cancer. The datasets were taken from 408 high-grade, muscle-invasive urothelial bladder carcinomas.
The researchers also found that the claudin-low tumours contained a group of gene signatures, which showed the immune system had penetrated the tumours, although the cancerous cells had subsequently blocked the immune cells’ checkpoint molecules.
Checkpoint inhibitor drugs can be used to de-repress the immune system where these molecules have been shut-down by cancerous cells. In light of the findings of this study, these drugs could prove invaluable in the treatment of metastatic tumours in the bladder.
The authors concluded: “These findings suggest that claudin-low bladder cancers may be particularly responsive to immunotherapy-based treatments that de-repress the immune system. Future studies will be needed to clinically test immune checkpoint inhibitors in this population.”