Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition marked by persistent inattention, hyperactivity, and impulsivity. Despite its considerable global prevalence, key gaps remain in our understanding of the structural and molecular changes underlying ADHD which complicate adult diagnosis, as symptoms present differently from those observed during childhood ADHD. On the other hand, while psychostimulants effectively mitigate some symptoms, significant controversy surrounds their long-term effects on cognition, learning, and memory, and day-to-day living. Moreover, our understanding of how various medications given to alleviate ADHD symptoms during pregnancy impact the developing fetal brain also remains largely unexplored. Here, we discuss the subtle differences between ADHD in children and adults and how these symptoms alter brain development and maturation. We further examine changes in monoamine signaling in ADHD and how psychostimulant and non-pharmacological treatments modulate these neural networks. We evaluate and discuss findings as they pertain to the long-term use of ADHD medications, including in utero exposure, on cognitive outcomes, and contextualize these findings with mechanistic insights from animal models.

Antibody-drug conjugates (ADCs) have transitioned from clinically marginal agents into a defining therapeutic class for solid tumor oncology. In DESTINY-Breast03, trastuzumab deruxtecan achieved a four-fold progression-free survival advantage over trastuzumab emtansine, attributable not to antibody engineering but to the linker-payload axis: a cleavable peptide linker and a topoisomerase I payload with bystander activity. Sacituzumab govitecan extends the same logic to Trop-2-positive disease via extracellular payload release, and the framework now spans breast, urothelial, gynecologic, lung, gastric, and colorectal cancers, with enfortumab vedotin plus pembrolizumab displacing platinum chemotherapy as first-line therapy for urothelial cancer in EV-302 (median overall survival 31.5 versus 16.1 months). This review synthesizes ADC biology along three analytical axes. The mechanistic axis links each linker-payload-DAR configuration to a specific tumor-biology barrier: vascular limitation, which delivers approximately 0.1% of the administered dose to tumor tissue; the binding-site barrier, which concentrates exposure at the perivascular margin; and antigen mosaicism, which defeats internalization-dependent killing. The translational axis examines resistance as a coordinated failure across antigen modulation, trafficking, efflux, apoptotic execution, and lysosomal processing. The clinical axis traces the platform’s migration toward earlier-line and curative-intent settings. We close by examining whether the ADC delivery architecture translates to precision immunosuppression in autoimmune disease, where the glucocorticoid receptor modulator ADC ABBV-154 met placebo-controlled efficacy endpoints in rheumatoid arthritis but was discontinued because its benefit-risk profile did not differentiate it from existing biologic therapies.

Attention deficit/hyperactivity disorder (ADHD) is a neurodevelopmental condition marked by persistent inattention, hyperactivity, and impulsivity. Despite its considerable global prevalence, key gaps remain in our understanding of the structural and molecular changes underlying ADHD which complicate adult diagnosis, as symptoms present differently from those observed during childhood ADHD. On the other hand, while psychostimulants effectively mitigate some symptoms, significant controversy surrounds their long term effects on cognition, learning and memory, and day to day living. Moreover, our understanding of how various medications given to alleviate ADHD symptoms during pregnancy impact the developing fetal brain also remains largely unexplored. Here, we discuss the subtle differences between ADHD in children and adults and how these symptoms alter brain development and maturation. We further examine changes in monoamine signaling in ADHD and how psychostimulant and non pharmacological treatments modulate these neural networks. We evaluate and discuss findings as they pertain to the long term use of ADHD medications, including in utero exposure, on cognitive outcomes and contextualize these findings with mechanistic insights from animal models.