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Precision Medicine in Urothelial Carcinoma: Current Markers to Guide Treatment and Promising Future Directions

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Opinion statement

The treatment landscape for urothelial cancer has changed dramatically in the last 10 years, with the approval of several new treatments. At the same time, profiling of individual tumors has become more commonplace with widespread availability of molecular testing and immunohistochemistry. For urothelial cancer, this has led to current guidelines recommending that molecular testing be obtained in the metastatic setting, and that it be considered in the setting of locally advanced disease. Between molecular testing and immunohistochemistry testing of tumors, the only current guideline-directed application of these tests is in the identification of FGFR3 or FGFR2 alterations for use of FGFR inhibitors. While additional recurrent molecular alterations linked to the pathogenesis of urothelial cancer have been identified, the ability to successfully “drug” the pathways association with such alterations remains limited. There has been extensive research into whether expression of particular proteins might inform specific treatment approaches such as the use of PD-L1 testing to guide immune checkpoint blockade. With the integration of antibody-drug conjugates into the treatment armamentarium for urothelial cancer, ongoing research is seeking to determine whether expression of the targets of these therapies, such as Nectin 4, Trop-2, or HER2, could help to guide treatment.

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  1. Division of Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai/Tisch Cancer Institute, New York, NY, 10029, USA

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MDG: Research funding - Bristol Myers Squibb, Novartis, Dendreon, Astra Zeneca, Merck, Genentech. Advisory Board/Consultant - Bristol Myers Squibb, Merck, Genentech, AstraZeneca, Pfizer, EMD Serono, SeaGen, Janssen, Numab, Dragonfly, GlaxoSmithKline, Basilea, UroGen, Rappta Therapeutics, Alligator, Silverback, Fujifilm, Curis, Gilead, Bicycle, Asieris, Abbvie, Analog Devices, Veracyte. EJM has no relevant financial or non-financial interests to disclose.

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Miller, E.J., Galsky, M.D. Precision Medicine in Urothelial Carcinoma: Current Markers to Guide Treatment and Promising Future Directions. Curr. Treat. Options in Oncol. 24, 1870–1888 (2023). https://doi.org/10.1007/s11864-023-01151-7

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