Copyright: © 2026 Aleid et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Immune checkpoint inhibitors (ICIs) deliver durable benefit to only a subset of patients and can be limited by immune-related adverse events (irAEs). The gut microbiome has emerged as an actionable, host-level modulator of ICI drug sensitivity and toxicity. This mini-review links microbial ecology to antigen presentation, T-cell priming and fitness, metabolite signaling, and barrier inflammation, and summarizes interventional evidence across three modalities. Responder-derived fecal microbiota transplantation (FMT) provides the strongest proof-of-concept for re-sensitization in anti-PD-1-refractory melanoma. Microbiome repair can also improve refractory ICI-associated colitis. Early trials of live biotherapeutics and defined consortia support scalability but highlight context dependence and design pitfalls, including antibiotic preconditioning. We discuss practical determinants of reproducibility, including co-medications, diet, engraftment and functional readouts, and conclude with safety, regulatory, and reporting priorities for clinically deployable microbiome engineering.

To evaluate the efficacy and safety of anlotinib combined with programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) inhibitors in the treatment of malignant solid tumors.

Locally advanced or metastatic urothelial carcinoma (la/mUC) is associated with poor prognosis and limited treatment options. Antibody-drug conjugates (ADCs) have emerged as a promising therapeutic approach. While previous meta-analyses have shown the efficacy and safety of ADCs in UC, the rapid development of new ADC agents and combination therapies necessitates an updated and comprehensive evidence synthesis.

Ulcerative colitis (UC), a major form of inflammatory bowel disease, has a global incidence of ~10.6 per 100,000 individuals. The long‑term side effects and dependency issues associated with conventional UC therapies have become increasingly evident, highlighting the need for more effective and safer treatment options. In previous years, clinical research on small‑molecule targeted drugs against UC has achieved notable progress; however, the underlying pathogenesis and therapeutic mechanisms of UC still require deeper investigation. The receptor for advanced glycation end products (RAGE) is a pattern recognition receptor that binds both pathogen‑associated molecular patterns and damage‑associated molecular patterns, thereby mediating inflammatory and cellular stress responses. Concurrently, vascular endothelial growth factor (VEGF), a key regulator of angiogenesis, is markedly upregulated in patients with UC and associates with disease severity. The RAGE/VEGF signaling axis has thus emerged as a notable target for antiangiogenic therapy in UC. Interventions aimed at disrupting the interaction between RAGE and its ligands, inhibiting RAGE pathway activation or suppressing VEGF upregulation have demonstrated promising potential to alleviate symptoms and slow disease progression. The present review summarizes previous advances in UC‑targeted therapeutics and elucidates the role of the RAGE/VEGF axis in UC pathophysiology, highlighting the potential mechanisms and clinical prospects of antiangiogenic strategies targeting this pathway.

Antiangiogenic combination therapy-antiangiogenic agents combined with immune checkpoint inhibitors and/or chemotherapy-has become an important treatment strategy for advanced driver-negative non-small cell lung cancer (NSCLC). We conducted a network meta-analysis to compare efficacy and safety and identify optimal antiangiogenic combinations.

In this article, we discuss the clinical and histopathologic findings of cutaneous adverse reactions to newer medications, including those recently approved to treat inflammatory skin diseases, such as dupilumab for atopic dermatitis and IL-12/-23 and IL-23 specific inhibitors for psoriasis, as well as those with oncologic indications, including immune checkpoint inhibitors, mogamulizumab, and enfortumab vedotin.

Marine organisms are a valuable source of lead compounds for drug development, and basic research. This field has been active for nearly half a century. However, because of their unique structures and poor chemical stability, it is difficult to achieve a sustainable, large-scale supply of marine natural products and thus, their use in drug development is rare. Renieramycin was first reported in 1982 by Fricke and Faulkner as a trace secondary metabolite from the blue sponge Reniera sp. Dimeric 1,2,3,4-tetrahydroisoquinoline derivatives, such as renieramycins, have attracted attention as novel anticancer agents. Therefore, challenges related to chemical stability and transformations, as well as development of total syntheses were overcome. Several excellent reviews on renieramycin marine natural products have been published. Research in the renieramycin family has been developed based on the results of various previous studies on saframycin, an antibiotic discovered from the Actinomycete Streptomyces lavendulae No. 314. In this review, we will introduce from a new perspective the results of ongoing efforts in the medicinal chemistry. We will explore the discovery, chemical transformation, total synthesis, and structure-activity relationships of renieramycin marine natural products, highlighting unexpected findings that emerged during the research process.1.

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of cancer therapy. Patients who experience CIPN can develop symptoms in their hands and feet, which may affect function and quality of life. Cryotherap.

Hyperthermia has been used as an adjuvant therapy alongside radiotherapy and chemotherapy for cancer treatment in some countries. However, since the 2000s, growing evidence has indicated that hyperthermia exerts regulatory effects not only on cancer cells but also on stromal immune cells and the research interest in this topic has grown notably in the current "era of immunotherapy". Of particular interest to oncoimmunologists and hyperthermia researchers, recent studies have shown that hyperthermia modulates the expression of a wide range of immune checkpoint and co-stimulatory molecules. In addition to the PD-1/PD-L1 and CTLA-4/CD80/CD86 checkpoints previously reported and intensively discussed in existing reviews, recent studies indicate that hyperthermia exerts a broader regulatory effect on many other checkpoint and co-stimulatory molecules, include TIGIT/CD155, Tim-3/Gal-9, OX40/OX40L, and 4-1BB/4-1BBL on T cells, CD47/SIRPα on macrophages, and CD40/CD40L on dendritic cells. The present review aims to provide a complementary update, focusing specifically on recent advances in understanding how hyperthermia regulates the expression of these newer targets, as well as preclinical evidence for combining hyperthermia with novel therapeutic agents targeting these molecules. The insights gained from these preclinical studies could serve as a valuable foundation for future experimental investigations and clinical translation.

Urological Cancers pose a serious threat to human health and represent a major challenge to healthcare systems worldwide. Among these, bladder cancer (BC), prostate cancer (PCa), and renal cancer (RC) are the most prevalent. Primary clinical management involves local or radical resection. However, for patients with advanced or inoperable disease, as well as those at high risk of post-surgical recurrence, chemotherapy remains an essential alternative or adjuvant treatment. Nevertheless, the lack of tumor targetability leads to low bioavailability and significant side effects of drugs, limiting the clinical application of chemotherapeutic agents. In recent years, plant lectins have gained significant attention in cancer therapy research owing to their unique tumor-recognition capabilities. Unlike traditional chemotherapeutic agents, they inherently bind specifically to abnormal glycans on urological tumor cells, endowing them with unparalleled targeted therapy advantages and great potential to address traditional chemotherapy's core limitations and improve clinical outcomes. This paper presents a systematic, comprehensive and structured review with integrated critical analysis of the progress in this field. It first describes the clinical treatment methods for common urinary system tumors, including an analysis of the importance and limitations of chemotherapy. It then elaborates on the biological activities and antitumor mechanisms of plant lectins, highlighting on recent advances in the use of native lectins and lectin-modified drug delivery systems (DDS) for treating these malignancies. Finally, based on full collation and overall understanding of the existing literature, the application limitations of plant lectins are summarized, and their prospects are discussed.

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by thrombosis in arteries, veins or small blood vessels, and/or obstetric APS (OAPS), as well as persistent positive antiphospholipid antibodies. In recent years, some authors have proposed that the pathogenesis of APS is closely related to activation of vascular endothelial cells, immune cells, and complement activation. However, further exploration is still needed. Previous studies have shown that the mammalian target of rapamycin (mTOR) is associated with pro-inflammatory and pro-coagulant processes. This indicates that the activation of the mTOR signaling pathway may function as an intermediate mediator, causing immune disorders, thereby leading to thrombosis and OAPS. Therefore, we should correctly understand the potential pathogenic role of the mTOR signaling pathway in APS, which will be more conducive to clinicians' understanding of the pathogenesis of this disease and the search for new therapeutic targets. We hope this can open up a new window for the management of APS.

Pharmacovigilance has revealed an alarming correlation between certain medications and a higher risk of cancer. In this narrative review, included research from 2020 to 2025, along with a few seminal older studies, so that it provides a clear picture of which drugs actually set off cancer and mechanisms involved at the molecular level. An extensive literature review of the subject was designed on PubMed, Embase, Scopus, and Web of Science using systematic search. Search words and phrases included: "Carcinogenic drugs," "drug-induced cancer," "medication-induced carcinogenesis," "immunosuppressant cancer risk," "hormone therapy and cancer," "chemotherapy-induced secondary malignancies," and names of relevant drugs.

This network meta-analysis evaluated the efficacy of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists, with or without Dexamethasone (D), for preventing chemotherapy-induced nausea and vomiting (CINV) in patients undergoing highly emetogenic chemotherapy (HEC) who were limited to these regimens.

Pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies, exhibits a 5-year survival rate below 10% and extremely poor clinical prognosis. Over 90% of PDAC patients harbor KRAS gene driver mutations, which promote tumor proliferation, invasion, and immunosuppression of the tumor microenvironment through constitutive activation of downstream RAF/MEK/ERK and PI3K/AKT/mTOR signaling pathways. Although the therapeutic potential of targeting KRAS has been recognized for decades, its smooth protein structure and lack of traditional drug-binding pockets led to its long-standing classification as an "undruggable" target, resulting in limited efficacy of early targeted agents. Recent breakthroughs with next-generation KRAS inhibitors have transformed the therapeutic landscape for pancreatic cancer. This review synthesizes evidence from basic research and clinical translation to provide a theoretical foundation and practical guidance for the precision treatment of KRAS-mutant pancreatic cancer.

Immune checkpoint inhibitors (ICPis) are associated with islet function impairment (IFI), manifesting as hyperglycemia, diabetes mellitus (DM), or diabetic ketoacidosis (DKA). Delayed detection and management may lead to irreversible β-cell damage and life-threatening complications. We conducted a systematic review and meta-analysis to assess the risk of IFI associated with ICPis.

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract, with its pathogenesis primarily linked to activating mutations in the KIT or platelet derived growth factor receptor alpha (PDGFRA) genes. Surgical resection remains the standard curative treatment for localized GIST; however, ~50% of patients eventually develop recurrence or metastasis. Since the introduction of imatinib in the early 21st century, the management of metastatic GIST has shifted from solely surgical intervention to a systemic, chronic disease management model centered on tyrosine kinase inhibitors (TKIs). However, during the course of treatment, most patients develop drug resistance. Despite the transformative impact of TKIs, some critical clinical challenges remain unresolved. Intratumoral heterogeneity, in particular, poses a significant obstacle, as tumors often comprise diverse populations of cells with varying genetic and molecular profiles. This diversity means that while some subclones may initially respond well to TKI therapy, others harboring inherent or acquired resistance mutations can continue to proliferate, ultimately leading to treatment failure. Additionally, the limited durability of TKIs responses, even in tumors initially sensitive to treatment, remains a pressing concern. Moreover, the lack of curative systemic options for advanced GIST, along with adverse drug reactions, underscores the unmet needs within this patient population. These challenges underscore the necessity of this review, which discusses current standard drug treatment strategies for advanced GIST, including sequential TKIs therapy and investigations into mechanisms of drug resistance. Finally, the review explores precise and actionable future directions for GIST drug development and clinical management, including mutation-stratified therapeutic sequencing, rational TKI-based combination regimens, and circulating tumor DNA (ctDNA)-guided real-time treatment monitoring and resistance surveillance.

Restoring apoptosis in malignant cells represents a central goal of anticancer therapy. Tumour cells often escape cell death by overexpressing anti-apoptotic members of the BCL-2 protein family, particularly BCL-2, BCL-xL, and MCL1. These proteins inhibit the intrinsic mitochondrial apoptotic pathway through intricate interactions with pro-apoptotic partners and direct modulation of the mitochondrial outer membrane. Their pivotal role in cell survival has established them as attractive therapeutic targets. Over the past two decades, significant efforts have been devoted to developing selective small-molecule inhibitors capable of neutralising these proteins and reactivating apoptosis. A first milestone was the discovery of ABT-263 (navitoclax), a dual BCL-2/BCL-xL inhibitor. Building on this achievement, the development of venetoclax, a highly selective BCL-2 inhibitor, marked a major breakthrough, demonstrating potent pro-apoptotic activity and clinical efficacy in several leukaemia subtypes. Despite these advances, the design of inhibitors of BCL-2 family members remains challenging, largely due to the structural characteristics of the BH3-binding groove, which is both shallow and hydrophobic, complicating the identification of molecules with optimal binding affinity and selectivity. PROTACs targeting BCL-xL may represent a promising future strategy, potentially overcoming the intrinsic limitations of small molecule inhibitors.

The menin-lysine methyltransferase 2A acute leukemia (KMT2A) protein-protein interaction has emerged as a clinically validated epigenetic target in acute leukemia, following the approval of the reversible menin inhibitor Revumenib for KMT2A-rearranged and nucleophosmin 1 (NPM1)-mutant disease. This success transformed a once "undruggable" interface into a tractable binding pocket, triggering the rapid expansion of medicinal-chemistry strategies aimed at achieving deeper and more durable transcriptional reprogramming. This review analyzes the full menin-inhibitor landscape from a medicinal-chemistry perspective, integrating reversible, covalent, and degrader-oriented modalities within a unified structure-activity framework. We highlight how scaffold architecture, pocket occupancy, electrophile placement toward Cys329, and polarity tuning control binding mode, residence time, metabolic stability, resistance susceptibility, and pharmacodynamic durability. Across all chemical classes, sustained target engagement-rather than equilibrium affinity alone-emerges as the dominant determinant of antileukemic efficacy. By integrating structure-activity relationship (SAR), resistance mechanisms, safety considerations, and translational scope across oncology and metabolic indications, this review provides a roadmap for the rational design of next-generation menin inhibitors and establishes menin as a model system for modern epigenetic drug discovery.

Marine organisms are considered as a reservoir of diverse metabolites with unique skeletons and multifaceted biological activities. Marine organisms, including Xenia, Cespitularia, and Heteroxenia, have been extensively studied in recent decades to explore their activities. Species of the genus Heteroxenia play a robust ecological role and afford a wide array of metabolites, including steroids, sesquiterpenoids, diterpenoids, and lipid derivatives with notable bioactivities as cytotoxic, antiviral, antimicrobial, and anti-inflammatory properties primarily based on in vitro studies. Fourteen compounds were isolated and their structures were elucidated based on NMR data and mass spectrometry. Most of these metabolites possess rare or uncommon structural frameworks such as gorgostane- and androstane-type steroids, and verticillane diterpenoids with an unusual C-6/C-12 skeleton, which are infrequently reported from marine sources. This review provides a comprehensive overview of Heteroxenia corals, highlighting their ecological role, metabolites isolated from Heteroxenia species, with emphasis on their 13C NMR spectroscopic features and reported bioactivities. This integrative approach provides a chemotaxonomic spectroscopic framework and identifies research gaps, that support future natural product discovery and pharmacological investigations of Heteroxenia species, while acknowledging that ecological function and general bioactivity do not necessarily predict direct therapeutic applicability and require further validation of selectivity and safety.