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.
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.
