Renal cell carcinoma (RCC), especially clear cell RCC (ccRCC), remains difficult to control after resistance to targeted therapy or immune checkpoint blockade develops. Cyclic peptides provide conformationally constrained and chemically adaptable scaffolds for direct target modulation, tumor-selective payload delivery, radiotheranostics, supramolecular assembly, and induced-proximity pharmacology. This focused mini-review groups cyclic peptide-based strategies according to the role played by the peptide in the therapeutic system. The peptide may act as the drug itself, carry a drug or radionuclide, guide a larger carrier, assemble into a drug-delivery material, or bring two proteins together. Direct RCC evidence is anchored by carbonic anhydrase IX (CAIX)-targeted DPI-4452/ZH2 radiotheranostics, cyclic Arg-Gly-Asp (cRGD)-guided small interfering RNA (siRNA) delivery to tumor endothelium, and PB1-p62-mediated polybromo 1 (PBRM1) degradation and immune sensitization. Drug-resistant non-RCC models are retained only as transferable design evidence for efflux-evasive or self-assembling delivery. We further discuss target heterogeneity, linker and assembly stability, pharmacokinetics, renal distribution, scalable synthesis, and the experimental controls required to attribute benefit to the cyclic peptide component. Although clinical therapeutic evidence remains limited, the emerging RCC-specific studies support a mechanism-matched development strategy for this drug class.

Cisplatin resistance remains a major hurdle in non-small cell lung cancer (NSCLC) treatment. Here, we designed and synthesized a novel ruthenium-based compound, which selectively kills cisplatin-resistant NSCLC cells while sparing parental cells. Mechanistically, Ru3 triggers mitochondrial damage and reactive oxygen species (ROS) accumulation. In addition, it upregulates the transcription factor E2F2, which directly represses IGFBP3 expression. IGFBP3 normally scavenges ROS via the GPX4 system; thus, E2F2-mediated IGFBP3 suppression disrupts this antioxidant defense, exacerbating ROS levels and cell death. Notably, cisplatin-resistant cells exhibit elevated GPX4 and IGFBP3 expression, making them particularly vulnerable to Ru3. This study elucidates the E2F2-IGFBP3-GPX4 axis as a novel therapeutic vulnerability and highlights Ru3 as a promising agent for refractory NSCLC.

Lysosome-dependent cell death (LDCD) is a distinct mode of regulated cell death, which differs from canonical cell death pathways such as apoptosis and necrosis. Its key features include lysosomal membrane permeabilization and the downstream signaling cascades triggered by cathepsin release. Recent studies have demonstrated that LDCD exerts dual, intricate influences on cancer initiation, progression, immune homeostasis and therapeutic responses. It not only confers a survival advantage upon cancer cells but also represents a promising target for targeted antitumor therapy. This review systematically summarizes the molecular mechanisms underlying LDCD, its dual regulatory roles in cancer, and LDCD-based anticancer therapeutic strategies, and outlines future research directions. Ultimately, this work sheds light on the mechanistic link between LDCD and oncogenesis, providing a rationale for the development of targeted antitumor strategies.

Novel anti-CD20 monoclonal antibodies have been developed to optimize B-cell depletion. A key mechanism of action of these therapeutic monoclonal antibodies is the activation of immune cells via Fc receptors (FcγR). B-cell depletion with anti-CD20 monoclonal antibodies was initially developed for the treatment of B-cell lymphoma. Subsequently, its use was extended to autoimmune diseases. Rituximab has long been the main monoclonal antibody used to treat immune-mediated glomerulopathies. In glomerular diseases, rituximab was initially used to treat membranous nephropathy, demonstrating a better safety profile compared to conventional immunosuppressive therapies and a good treatment response. Therefore, other drugs targeting the same therapeutic receptor, anti-CD20, have been developed. This review aims to highlight, from a comprehensive perspective, the different anti-CD20 agents available to date.

Interleukin 23 (IL-23) is a key mediator of immune-mediated intestinal inflammation and plays an important role in the pathogenesis of inflammatory bowel disease. Inhibition of IL-23 signaling has therefore been validated as a therapeutic target in IBD. Here, we tested small binding proteins of non-immunoglobulin origin targeting either the IL-23 cytokine p19 subunit or the IL-23 receptor subunit IL-23R, designated ILP and REX binders, respectively. ILP317 and REX115 variants of formerly identified protein collections were tested in murine experimental colitis. Lactococcus lactis bacteria engineered for ILP317 or REX115 expression were administered to experimental mice via yogurt-coated food pellets before and during dextran sulfate sodium (DSS) and trinitrobenzenesulfonic acid (TNBS)-induced colitis. To compare both protein blockers, ILP317 and REX115 binders were administered intraperitoneally as soluble recombinant proteins. General health status, colon macroscopic and histological changes, mucosal tissue cell infiltration, local and systemic inflammatory cytokines were analyzed. In DSS- and TNBS-induced colitis, intraperitoneal administration of soluble ILP317 or REX115 reduced disease severity, including disease activity index, colon shortening, and mucosal inflammatory cell infiltration. Oral administration of recombinant L. lactis expressing ILP317 also showed consistent protective effects, whereas oral L. lactis expressing REX115 produced less pronounced effects in several experimental settings. Overall, ILP317 appeared more effective than REX115 when delivered orally by recombinant L. lactis. Oral administration of non-colonizing L. lactis expressing an IL-23p19 inhibitor may represent a promising preclinical strategy for the development of novel, non-invasive approaches to modulate intestinal inflammation.

Sleep deprivation (SD) impairs cognitive function through oxidative stress, neuroinflammation, and neuroendocrine dysregulation, whereas recovery sleep may not fully reverse these alterations. Silibinin possesses antioxidant, anti-inflammatory, and neuroprotective properties; however, its potential to facilitate recovery following prolonged SD remains unclear. This study investigated the effects of silibinin on cognitive dysfunction and hippocampal alterations induced by 5 days of SD, with or without a subsequent 24-h recovery period, in rats. Forty-eight adult male rats were allocated to control (n = 16), SD (n = 8), SD + recovery (n = 8), SD + silibinin (n = 8), and SD + silibinin + recovery (n = 8) groups. Cognitive performance was assessed using the Open Field Test, Morris Water Maze, and Y-Maze. Serum oxidative stress (MDA and SOD), inflammatory (TNF-α and IL-6), and hormonal biomarkers were evaluated. Hippocampal BDNF and CaMKII levels, histopathological changes, and the immunohistochemical expression of PCNA, synaptophysin, and GFAP were also assessed. SD significantly impaired cognitive performance (P < 0.05), increased oxidative stress and inflammatory cytokines (P < 0.01), altered stress-related hormones (P < 0.05), decreased hippocampal BDNF and CaMKII levels (P < 0.001) and induced marked histopathological and immunohistochemical changes. A 24-h recovery period partially ameliorated these alterations. Silibinin treatment significantly attenuated the SD-induced behavioral, biochemical, hormonal, histopathological, and immunohistochemical alterations (P < 0.05), with further improvement following recovery sleep (P < 0.05), restoring most parameters to levels comparable to those of the control group. These findings suggest that silibinin protects against SD-induced cognitive dysfunction and hippocampal injury by attenuating oxidative stress, neuroinflammation, and neuroendocrine disturbances while enhancing recovery during subsequent recovery sleep.

Curcumin has various biological effects, but its poor aqueous solubility limits its practical use. This study investigated the effects of curcumin-loaded nanospheres (CN) on cellular injury induced by fine dust (PM10) in HaCaT human keratinocytes and examined the signaling mechanisms involved. PM10 exposure significantly decreased cell viability, whereas CN at 10[-4] μg/mL significantly restored cell viability and showed a protective effect at a lower concentration than unformulated curcumin. PM10 rapidly increased intracellular reactive oxygen species (ROS) levels, followed by activation of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (MAPK), and nuclear factor-kappa B (NF-κB). CN reduced ROS generation and inhibited activation of these signaling molecules. CN also restored the altered Bax/Bcl-2 balance, decreased caspase-3 cleavage, and reduced caspase-1-dependent IL-1β processing in PM10-exposed cells. Treatment with NAC and inhibitors of ERK, p38 MAPK, NF-κB, and caspase-1 further reduced PM10-induced cytotoxic and inflammatory responses, supporting the involvement of these pathways. Overall, CN attenuated fine dust-induced cellular toxicity in keratinocytes by suppressing ROS-dependent MAPK/NF-κB signaling and downstream apoptotic and inflammatory responses.

Antibody-drug conjugates (ADCs) have established targeted payload delivery as an important anticancer strategy, but their efficacy remains constrained by antigen heterogeneity, incomplete internalisation, resistance and dose-limiting toxicity. Bispecific antibody-drug conjugates (BsADCs) add a second antigen- or epitope-binding specificity with the aim of broadening tumour coverage or altering receptor trafficking. The field crossed a major translational threshold in 2026, when izalontamab brengitecan (iza-bren; BL-B01D1), an EGFR×HER3 BsADC, received its first regulatory approvals in China for previously treated recurrent or metastatic nasopharyngeal carcinoma and oesophageal squamous cell carcinoma, while phase III studies also showed survival benefit in triple-negative breast cancer. These developments shift the central question from whether bispecificity can produce antitumour activity to when it can generate a clinically meaningful therapeutic window. This review evaluates BsADC development through six linked determinants: target-pair biology and co-expression, binding geometry and avidity, internalisation and lysosomal trafficking, linker-payload chemistry and drug-to-antibody ratio, intratumoural distribution and bystander activity, and biomarker-guided dosing and patient selection. We further examine how payload-mediated immunogenic cell death, Fc/Fcγ receptor-dependent uptake, suppressive tumour-immune niches and checkpoint-based combinations may modify activity beyond target recognition. Clinical programmes illustrate divergent outcomes: iza-bren provides regulatory validation of the modality, whereas experience with MEDI4276, zanidatamab zovodotin and REGN5093-M114 shows that enhanced binding or internalisation does not guarantee sustainable development. Importantly, much of the mechanistic and combination evidence for immune activation still derives from monospecific ADCs; immune benefit should therefore not be attributed to bispecificity itself without direct evidence. Future progress should integrate human pharmacokinetic/pharmacodynamic data, target-pair and immune-contexture biomarkers, dose-exposure-toxicity relationships and comparative value over optimized monospecific ADCs.