# Current Landscape and Evolving Role of Targeted Agents in Urothelial Carcinoma

## TL;DR

This review summarizes current and future targeted therapies for urothelial carcinoma, focusing on molecular targets and their clinical impact.

## Contribution

The paper provides a comprehensive overview of emerging targeted agents and their potential to improve outcomes in urothelial carcinoma.

## Key findings

- FGFR inhibitors and Nectin-4-directed antibody–drug conjugates show clinical promise in urothelial carcinoma.
- Immune checkpoint inhibitors improve prognosis but benefit only a subset of patients.
- Molecular characterization is key to identifying new therapeutic targets like HER2.

## Abstract

Despite the availability of various treatments, such as chemotherapy and immunotherapy, urothelial carcinoma remains a disease with a poor prognosis. In recent years, greater biological knowledge has led to the identification of new therapeutic targets, in order to improve survival of these patients by personalizing their systemic treatment. In this review, we aim to collect the main available data about the efficacy and safety of target treatments in urothelial carcinoma, also focusing on their possible future applications.

Urothelial carcinoma represents one of the deadliest urological tumors, due to its biological aggressiveness and the ephemeral response to platinum-based chemotherapy of advanced-stage disease. The use of immune checkpoint inhibitors has positively impacted the prognosis of these patients, although only a proportion of them achieve long lasting disease control. As with other solid tumors, in the last decade, there has been a growing interest in the molecular characterization of urothelial carcinoma in order to identify new therapeutic targets and improve survival in these patients. The aim of this narrative review is to summarize the main evidence available in the literature concerning the role of targeted therapies in urothelial carcinoma, especially focusing on related molecular targets, published data on clinical efficacy, and on future perspectives. Specifically, the effort of this review aims to strengthen the clinical impact of well-known molecular patterns and relative target treatments (such as FGFR inhibitors and Nectin-4-directed antibody–drug conjugates) and to examine the role and preliminary data of drugs targeting biomarkers that are not yet commonly used in clinical practice (such as HER2).