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.

Combined inhibition of FGFR1 and MET significantly suppressed tumor growth in resistant cells. These findings establish MET amplification and GAB1-SHP2 signaling as central mediators of erdafitinib resistance in FGFR1-amplified MIBC and support dual FGFR1/MET targeting as a promising therapeutic strategy.

This study presents the first integrated analytical method based on HPLC-MS/MS and HPLC-Orbitrap-HRMS for the in vitro metabolic assessment of gunagratinib. We anticipate the clinical application of this method in future pharmacokinetic or metabolism studies.

Functionally, the FGFR inhibitor erdafitinib suppressed cell proliferation and migration, and FGFR3 silencing also markedly reduced proliferation, migration, invasion, and colony formation in cancer cell lines. The down-regulation of FGFR3 in muscle-invasive bladder cancer, coupled with the inhibitory effect of its inactivation on cell growth, suggests a significant role for FGFR3 in bladder cancer progression.

These findings demonstrate the utility of patient-derived tumor models in the identification and the functional validation of potentially targetable molecular alterations in preclinical setting.

Awareness of these risks and early intervention can prevent vision loss. Further research is needed to explore underlying mechanisms and preventive strategies.