This has broadened the treatment landscape of the disease to include novel agents, such as antibody-drug conjugates (e.g., enfortumab vedotin) and targeted therapies, including the pan-fibroblast growth factor receptor (FGFR) inhibitor erdafitinib. Equally important is the standardization and timely implementation of FGFR3 testing in clinical practice to optimize treatment planning. This review addresses key considerations in FGFR3 testing in mUC and discusses how it can be routinely incorporated into clinical practice.

Furthermore, [68Ga]Ga-DOTA-cHW8 validated FGFR1 dynamic modulation during erdafitinib treatment in CDX and PDX models, establishing its efficacy for noninvasive UM treatment response assessment. This study reports a cyclic peptide-based radiotracer, [68Ga]Ga-DOTA-cHW8, for FGFR1 PET imaging in UM. Through rational design and preclinical validation in UM models, we establish its high specificity, favorable pharmacokinetics properties, and capability to monitor FGFR1 dynamics during targeted therapy.

P2, N=11, Terminated, M.D. Anderson Cancer Center | Trial completion date: Jun 2026 --> Feb 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2026 --> Feb 2026; <75% participation

P2, N=239, Active, not recruiting, Janssen Research & Development, LLC | Trial completion date: Dec 2026 --> Mar 2027

Survey-based opinions can effectively capture treatment selection preferences for mUC and could inform future clinical trial design. Additional data, including the impact of residual toxicity from 1L EVP, are needed to better understand real-world treatment sequencing patterns.

First-line erdafitinib monotherapy and erdafitinib plus cetrelimab demonstrated antitumor activity and a manageable safety profile in cisplatin-ineligible patients with mUC.

Recent development of selective FGFR inhibitors-such as pemigatinib, erdafitinib, and futibatinib-has translated mechanistic insights into measurable clinical benefits in genomically defined patient populations. This review also highlights emerging therapeutic modalities, such as antibody-drug conjugates and nanotechnology-based delivery systems, which may improve target specificity and prolong therapeutic durability. By integrating molecular, translational, and clinical evidence, this review aims to establish a comprehensive framework for precision oncology strategies targeting FGFR-driven malignancies.

Herein, we designed and synthesized a series of dual-functional compounds by conjugating the oxygen-mimicking moiety 2-methyl-5-nitroimidazole with the FGFR inhibitor Erdafitinib...These combined effects thereby enhanced tumor sensitivity to radiotherapy. Collectively, the findings support 19e as a potential therapeutic agent for the treatment of malignant tumors.

Pooled analyses confirm the robust efficacy of erdafitinib in a diverse population of pretreated patients with advanced/metastatic CCA harboring prespecified FGFR alterations. These findings are consistent with previously observed efficacy of FGFR-targeted agents in patients with CCA.

Recent advances in targeted therapies, including FGFR inhibitors (for example, erdafitinib) and antibody‑drug conjugates (ADCs) targeting Nectin‑4 (enfortumab vedotin) and HER2 (disitamab vedotin), have reshaped treatment paradigms. The present review synthesizes current evidence on molecularly guided therapies, contrasts resistance mechanisms between FGFR inhibitors and ADCs, and evaluates strategies to overcome therapeutic limitations. By integrating translational insights and emerging preclinical data, it was aimed to provide a roadmap for optimizing biomarker‑driven approaches, novel combinations and next‑generation agents for the treatment of UC.

P2, N=90, Recruiting, Spanish Oncology Genito-Urinary Group | Trial completion date: Mar 2029 --> Oct 2029 | Trial primary completion date: Mar 2026 --> Jul 2026

Enfortumab vedotin, a Nectin-4 targeting ADC, is now the first line therapy of choice in combination with pembrolizumab. Erdafitinib, a pan FGFR1-4 inhibitor, is approved for patients with susceptible FGFR3 alterations...We propose strategies for overcoming resistance including combination strategies, tumor microenvironment modification, and drug structure modification to maximize efficacy. The progress to date in mUC has been remarkable, but there is still significant work to do in this deadly disease and this review highlights the gap between current available therapeutics and cure that so desperately needs to be closed.