EAU 2018: Comprehensive Genomic Profiling of Neuroendocrine Bladder Cancer Pinpoints Molecular Origin and Potential Therapeutics
Zhang et al. evaluated bladder tissues and blood samples from patients with NEBC and compared them to known genetic profiles of conventional urothelial carcinoma of the bladder. Fascinatingly, they found that the mutational landscape of NEBC is very similar to conventional bladder cancer. They were even able to identify specific oncogene-addicted conventional tumor types that might be induced to form neuroendocrine-like tumor cells with the depletion of TP53 and RB1. This is the first high resolution overview of the genetic makeup of NEBC. Taken together, these findings suggest that NEBC arises from a common cellular origin as conventional bladder cancer.
NEBC is a dangerous cancer, but we now have evidence that it can arise from divergent differentiation within neoplastic urothelium. Because of its genetic similarity to urothelial carcinoma, there may be common pathways in early neoplastic differentiation that can be targeted effectively in both kinds of tumors. As the authors note, the radically different phenotypes are likely a result of the significant lineage segregation between the tumor types. Nonetheless, this study is a good first step in developing a deeper understanding of NEBC and identifying potential treatment targets that were not previously known.
Speaker: Zhang R
Written by: Shreyas Joshi, MD, Fox Chase Cancer Center, Philadelphia, PA, Twitter: @ssjoshimd, at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark