Metastatic urothelial carcinoma (mUC) is a lethal cancer with limited therapeutic options. Advances in genomic and transcriptomic research have deepened the understanding of mUC biology, leading to the identification of clinically relevant molecular alterations that represent potential actionable targets. 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. Genomic alterations in FGFR3 are well-established oncogenic drivers in bladder cancer and represent predictive biomarkers of response to FGFR-targeted therapies. The phase III THOR trial demonstrated the clinical benefit of erdafitinib in previously treated mUC patients harboring FGFR3 alterations and supported its subsequent approval by the European Medicines Agency. In this context, accurate molecular profiling is essential to guide patient selection for FGFR inhibitor therapy. 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.
Antibody-drug conjugates (ADCs) are a promising innovation in precision oncology, combining tumor-targeting antibodies with potent cytotoxic molecules to improve their therapeutic index and outcomes. This Series paper explores the evolution of ADCs from early development to current EMA-approved therapies, highlighting the key advances in design and mechanisms of action. We expand on the critical components of ADCs (linkers, antibodies and payloads) and how the evolution of the linker technologies, site-specific conjugation and novel payloads are increasingly enhancing their therapeutic index. Pivotal clinical trials in solid and hematologic cancers are summarised, alongside the caveats related to efficacy, safety and accessibility. Challenges such as narrow therapeutic windows driven by dose-limiting toxicities/off-target effects and high production costs are discussed, as well as future directions including combination therapies, overcoming resistance mechanisms, and biomarker-guided patient selection. The need for ongoing innovation and collaboration is key to maximizing the clinical potential of ADCs in Oncology.
To evaluate the long-term safety (≥12 months) of monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) or its receptor in migraine prevention by synthesising evidence from clinical trials and real-world studies. We focus on drug discontinuation due to adverse events and the type and frequency of adverse events. This is the first review to analyse the effects of the long-term use of all anti-CGRP (receptor) mAbs, aiming to provide novel insights for clinical practice and future treatment strategies. We systematically searched PubMed, Cochrane Library, and ClinicalTrials.gov for studies with ≥12 months of anti-CGRP (receptor) mAb use between January 2013 and April 2025. A random-effects meta-analysis of proportions (logit transformation, inverse variance weighting, restricted maximum likelihood) was performed to estimate pooled discontinuation and adverse event rates. Risk of bias was assessed using the ROBINS-I score. From a total of 1,499 records, 14 met the inclusion criteria and were eligible for data analysis. These 14 records corresponded to 11 individual studies with observational durations all exceeding 12 months. Seven studies investigated erenumab, two eptinezumab, and one each fremanezumab and galcanezumab. All studies were judged to have a severe risk of bias due to their underlying design. The overall pooled proportion of treatment discontinuation for any reason among patients receiving anti-CGRP (receptor) mAbs was 23
Healthcare is a sector that can greatly benefit from AI due to the critical nature of medical decisions and the demand for accuracy and efficiency. Advances in AI algorithms have shown promise in diagnosing conditions at early stages. To improve the transparency of such systems, Explainable AI (XAI) techniques have been explored. However, if not properly integrated, AI and XAI can introduce new challenges, such as reduced cognitive engagement or overreliance on AI-system outputs. While prior research has mainly focused on isolated tasks, such as AI-assisted diagnosis, this study takes a holistic approach by examining the impact of AI recommendations and explanations across multiple sequential decision points within clinical case scenarios. Thirty-four medical students completed two simulated clinical cases with varying levels of AI assistance. The scenarios reflected realistic workflows, requiring participants to prescribe diagnostic exams and make final diagnoses. Results indicate that AI recommendations and explanations can enhance medical performance but do not consistently improve efficiency. In simpler cases, AI assistance supported appropriate exam prescription and reduced decision-making time. In more complex cases, explanations significantly improved diagnostic accuracy but also led to higher resource use, with participants ordering more unnecessary exams.
Glycans are essential components of homeostatic networks, acting as fine tuners of immunological responses, and are therefore promising targets for manipulating immune tolerance. Glycans shield the entire gut mucosa surface, contributing to epithelial barrier integrity. Moreover, most microorganisms expose glycoconjugates on their surfaces, making glycans essential molecules in the crosstalk between host immune response and the gut microbiota. The vast amount of biological information encoded by mucosal glycans is deciphered by a variety of glycan-binding proteins that translate glycan recognition into either pro-inflammatory or anti-inflammatory responses. Current evidence from inflammatory bowel disease (IBD) has highlighted the prominent role of glycans in establishing and regulating key cellular and molecular pathways underlying the transition from health to intestinal inflammation, with implications for understanding IBD immunopathogenesis and for IBD prediction and prevention. In this Review, we discuss current advances, emerging challenges and future prospects in exploiting the power of the mucosal glycocalyx and the glycome as master coordinators of the immunoregulatory networks in IBD from the preclinical phase to established diagnosis. We discuss the clinical utility of the glycome as a serological biomarker with diagnostic, prognostic and predictive value, and as a potential new target for preventive intervention strategies in IBD. Glycans are essential components of the gut mucosa that modulate epithelial barrier integrity, host–microbiota interactions and gut immune response. This Review discusses the role of mucosal glycans in gut homeostasis, in intestinal inflammation and their therapeutic potential for inflammatory bowel disease.
