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DNA damage response as biomarkers informing a precision medicine approach to bladder cancer: what are the next steps?

Platinum-based chemotherapy has been standard care in both the perioperative and metastatic settings for the treatment of urothelial cancer of the bladder for decades. The armamentarium of treatment for advanced urothelial cancer has recently expanded with the development and regulatory approval of PD-1/PD-L1 inhibitors [1]. Despite such advances in the treatment of advanced urothelial cancer, the identification of molecular vulnerabilities to both older and newer therapies that may translate into predictive biomarkers in the clinic has proven elusive. However, the advent of high throughput RNA and DNA sequencing has provided an unprecedented picture of the genomic landscape of urothelial cancer. These efforts have revealed that, among other notable discoveries, molecular alterations in DNA damage response and repair (DDR) genes are much more common than previously recognized and remarkably that such alterations may confer sensitivity to not only platinum-based chemotherapy but also to immune checkpoint blockade [2].