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.

To assess the incidence of delayed chemotherapy-induced nausea and vomiting (CINV) and identify key risk factors among adult patients.

Thalidomide represents one of the most instructive case studies in modern medicinal chemistry, embodying both a historic pharmaceutical tragedy and a remarkable example of drug repurposing and molecular reinvention. Initially introduced as a sedative and antiemetic, its catastrophic teratogenic effects reshaped global drug regulatory frameworks. Decades later, renewed investigation uncovered potent immunomodulatory, anti-inflammatory and antiangiogenic activities, leading to its controlled clinical use in erythema nodosum leprosum, multiple myeloma and related disorders. Central to this renaissance was the identification of cereblon as a key molecular target, transforming thalidomide and its analogs into versatile chemical tools for targeted protein degradation. This review provides a comprehensive overview of thalidomide from a synthetic and medicinal chemistry perspective, covering classical and modern synthetic strategies, access to analogs, stereochemical considerations and asymmetric approaches. Particular emphasis is placed on thalidomide-derived cereblon binders in PROTACs and molecular glue technologies. Beyond protein degradation, the diverse biological activities of thalidomide are discussed, including modulation of cytokines, angiogenesis, and immune signaling pathways. Collectively, thalidomide exemplifies how mechanistic insight, synthetic innovation and careful risk-benefit evaluation can transform a once-discarded molecule into a cornerstone of contemporary drug design.

ADP-ribosyltransferases (ARTs) regulate key processes in cancer, including DNA repair, transcription, immune responses, and treatment resistance. The clostridial toxin-like ADP-ribosyltransferase (ARTC) family and the diphtheria toxin-like ADP-ribosyltransferase (ARTD) family play a crucial role in genomic stability by modification of proteins either with mono(ADP-ribosyl)ation (MARylation) or poly(ADP-ribosyl)ation (PARylation). These ARTs are promising therapeutic targets and could serve as biomarkers in cancer management. This review explores the roles of these enzymes and current knowledge on specific inhibitors. A literature search was conducted in PubMed and Google Scholar to identify studies published between 1992 and 2025 on ADP-ribosyltransferases and their roles in cancer. Among ARTC family, ART1 and ART3 modulate the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, influencing angiogenesis, tumor growth, and immune evasion via cluster of differentiation 8+ (CD8+) T-cell apoptosis. Within the ARTD family, poly(ADP-ribose)polymerase (PARP)1 and PARP2 are activated by DNA single-strand breaks and are clinically validated targets in cancers with homologous recombination deficiency, such as breast cancer susceptibility genes 1/2 (BRCA1/2)-mutated breast cancer. Their inhibition exemplifies synthetic lethality and has shown clinical efficacy. Four PARP inhibitors, olaparib, niraparib, rucaparib, are approved by the Food and Drug Administration (FDA) approved. Despite these advances, selective inhibitors for ARTs remain underexplored. Ongoing research focuses on overcoming PARP inhibitor resistance, improving biomarker-driven patient selection, and expanding therapeutic strategies that target ART-related pathways.

Vascular tumours and malformations encompass infantile hemangiomas (IHs) and genetically driven vascular malformations with distinct natural histories and therapeutic vulnerabilities. The discovery that the non-selective beta-blocker propranolol induces rapid regression of proliferating IHs established the first widely adopted systemic pharmacologic therapy in vascular anomaly care and provided a clinical proof-of-concept that targeting lesion-specific endothelial biology can alter disease course. In parallel, recurrent somatic variants affecting PI3K/AKT/mTOR (e.g., PIK3CA, TEK/TIE2, AKT1) and RAS/MAPK (e.g., KRAS, NRAS) signalling have reframed many malformations as mosaic disorders amenable to targeted inhibition with agents such as sirolimus, alpelisib, AKT inhibitors and MEK inhibitors. This review synthesizes translational mechanisms, clinical evidence and safety considerations for beta-blockers and emerging targeted therapies, emphasizing lesion phenotype, timing of intervention and molecular stratification as determinants of response. We highlight current limitations, including toxicity, durability and pathway escape, and outline future directions for precision therapy and genotype-guided trial design in vascular anomalies.

Drug resistance, also known as chemoresistance, is a known impediment in fighting cancers. Pak1 (p21-activated kinase), a serine/threonine kinase, is a known oncogene implicated in tumor progression and associated with poor prognosis in cancer patients. Pak1 has been reported to be mechanistically contributing to drug resistance to tamoxifen and gemcitabine. Using an integrative approach, the present study investigated Pak1 and its precise role in conferring chemoresistance alongside other known kinases. Study identified 25 additional kinases contributing to resistance to 12 commonly used drugs in clinics for the treatment of breast, head and neck, and pancreatic cancers. The study analysis revealed that mutated Pak1 and more than one kinase were likely to be involved in drug resistance in patients associated with poor prognosis. The study concluded that the detection of altered kinases in resistant tumors is imperative, and a combination of kinase inhibitors could be useful for treatment rather than single agents to improve treatment outcomes.

Increasing survival rates following cancer diagnoses, combined with demographic aging, have resulted in a growing population of long-term survivors. Many of these individuals face persistent and late-onset effects of oncological treatments. This article examines the most common sequelae associated with traditional treatment approaches, presents emerging evidence on innovative therapies, and explores their impact on patients' quality of life.

Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal solid malignancies, characterized by aggressive biology and a paucity of effective treatments. Activating mutations in KRAS occur in more than 90% of cases and are fundamental to tumor initiation, progression, therapeutic resistance, and immune exclusion, establishing KRAS as the dominant oncogenic driver in PDAC. Long considered undruggable, KRAS has recently become a viable therapeutic target with the development of allele-specific inhibitors as well as pan-RAS(ON) agents capable of broadly suppressing mutant RAS signaling. Preclinical models and early-phase clinical trials demonstrate meaningful antitumor activity, with emerging evidence of tumor microenvironment remodeling and delayed resistance. Combination strategies integrating KRAS-directed therapies with chemotherapy, vertical pathway inhibition, immunotherapy, and emerging approaches such as KRAS degradation and RNA-targeted approaches are being explored to improve the depth and durability of response. Together, these advances signal a paradigm shift toward molecularly guided treatment strategies in PDAC and offer a promising path forward in a disease with substantial unmet clinical need.

Neuro-ophthalmic complications associated with immune checkpoint inhibitors (ICIs) are rare. These involve adverse events primarily affecting the optic nerve, other cranial nerves, and the neuromuscular junction. Myasthenia gravis-like syndrome (often with concomitant myositis) is the most commonly reported immune-related adverse event, followed by optic neuropathy, of which the most notable is optic neuritis. Symptoms typically present within 6 months of exposure. Prompt and comprehensive evaluation is essential. Diagnostic work-up may include MRI brain and orbits, lumbar puncture, serum, and cerebrospinal fluid antibody testing.