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.

Oral systemic anti-cancer therapies improve convenience, but also shift responsibility for treatment management to the patient. Education, communication, and models of care must adapt to support safe, equitable, and sustainable oral anti-cancer treatment.

Chemotherapy-induced nausea and vomiting (CINV) is a common and severe adverse effect of breast cancer (BC) treatment that compromises treatment adherence and quality of life. This meta-analysis aims to assess the prevalence and risk factors of CINV in BC patients, thereby providing clinical insights for its prevention and improvement. Patient/material and methods: Relevant literature was identified through an extensive search of electronic databases from their inception up to July 10, 2025: PubMed, Web of Science, Embase, Cochrane, CNKI, Wanfang, and VIP databases on prevalence rates, odds ratios (OR), and corresponding 95% confidence intervals (CI) were extracted for analysis.

Although targeted therapy has made significant advances in cancer treatment throughout these years, drug resistance still remains a major obstacle. Plenty of evidence has proved that abnormal expression of receptor tyrosine kinase AXL is associated with targeted therapy resistance and poor clinical outcomes. AXL drives drug resistance through diverse mechanisms, including altering tumor cell phenotypes, orchestrating DNA damage response process, promoting the activation of bypass signals, or interacting with other receptor tyrosine kinases. Preclinical and clinical studies have demonstrated that combined inhibition of AXL and the other target can enhance the efficacy of various targeted therapies and improve outcomes for patients with drug resistance. This review summarizes recent advances in the specific roles of AXL in targeted therapy resistance and AXL-targeted treatment strategies. It further explores the potential clinical value of combinatorial approaches involving AXL inhibition and discusses future directions for its application in developing novel targeted therapies and advancing precision oncology treatment. 
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The aim of the present study was to investigate the prevalence of oral manifestations among patients undergoing chemotherapy.

Single-stranded DNA gaps (ssDNA gaps) have emerged as a potential indicator of therapeutic response in cancer. Accumulation of ssDNA gaps is associated with increased sensitivity of cancer cells to genotoxic therapies like PARP inhibitors (PARPi) and cisplatin chemotherapy. However, efficient repair or suppression of ssDNA gap formation is associated with therapy resistance and treatment failure. Therefore, understanding how ssDNA gaps form and are repaired can help identify biomarkers that can guide new treatment strategies to overcome resistance. In this review, we discuss different sources of ssDNA gap formation and the repair mechanisms that have been characterized to date. We bring together current knowledge on how these gaps are processed and what their ultimate fate may be. Finally, we discuss how established drugs like PARPi, hydroxyurea, and platinum compounds, induce and/or exploit ssDNA gaps. Throughout this review, we highlight ssDNA gaps as a potential therapeutic vulnerability that can be used to advance personalized cancer therapy.

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders driven in large part by aberrant activation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway via the JAK2 V617F and related mutations. The success of first-generation ATP competitive JAK2 inhibitors has validated JAK2 as a therapeutic target, yet clinical benefits remain constrained by issues of off target toxicity, limited mutation allele burden reduction, and the emergence of persistence or resistance. In this review, we focus on a rapidly emerging design paradigm: targeting novel binding sites on JAK2 beyond the canonical ATP pocket-including allosteric sites, covalent anchor residues, and pseudokinase regulatory domains. We summarize structural and computational insights into these new sites, compare mechanistic and therapeutic advantages (such as enhanced selectivity, reduced cross JAK inhibition and potential to overcome resistance) and evaluate preclinical and early clinical evidence. We further identify remaining challenges in the development of next generation JAK2 inhibitors-such as site validation, ligand residence time, covalent binding safety, and rational combination therapies-and propose future directions for translation into the MPN clinic. By refocusing the JAK2 inhibitor field around novel binding site exploitation, we suggest a path toward more potent, selective and enduring therapies for MPN patients.

The purpose of this review is to highlight recently published research that can provide insight into how either sex or chemotherapeutics can impact cancer regulation of muscle anabolic resistance. Critical knowledge gaps are emphasized that are linked to cancer and treatment disruptions to muscle anabolic signaling. We speculate and propose a rationale for estrogen's protective effect against cancer-induced muscle anabolic resistance in females. Furthermore, there is growing evidence that many cancer treatments have the potential to exacerbate muscle anabolic resistance in both males and females. We present current evidence and speculate on how nutritional interventions could serve as key modulators of cancer-induced anabolic resistance in these conditions.

Hepatocellular carcinoma (HCC) is a malignant tumor with a high mortality rate globally, ranking among the top cancers in incidence and posing a serious human health threat. In recent years, with research advancement in traditional medicine, traditional Chinese medicine (TCM) has attracted increasing interest for its potential role in the management of hepatocellular carcinoma (HCC). As a comprehensive review, this article critically synthesizes the biological mechanisms and clinical application evidence of TCM extracts and classic formulas in HCC treatment, systematically detailing the important roles and specific mechanisms of TCM in inhibiting tumor growth, inducing apoptosis, enhancing immunity, and suppressing angiogenesis. This review aims to synthesize and analyze existing findings to provide a consolidated theoretical basis and identify potential research gaps. Furthermore, it seeks to explore new therapeutic concepts by bridging TCM theory with modern pharmacological approaches, thereby promoting the development of integrated strategies in oncology. Ultimately, we aim to contribute to the improvement of patient survival rates and quality of life. However, while preclinical evidence is promising, the clinical evidence base requires further strengthening through larger-scale, rigorously designed trials to validate efficacy and establish standardized protocols.

The emergence of drug-resistant cancers has led to the discovery of novel therapeutic agents. Medicinal plants are a promising source, with Dendrophthoe pentandra (L.) Miq. a parasitic plant used in ethnomedicine, showing promising anticancer potential. This study reviews preclinical evidence of the anticancer activity of D. pentandra, focusing on its phytochemical constituents and molecular mechanisms of action. A systematic search of Scopus and PubMed databases was conducted for preclinical studies published between 2015 and 2025. After screening, 13 articles met the eligibility criteria and were included in narrative synthesis. The 13 included studies demonstrated that D. pentandra extracts exhibit potent cytotoxic and antiproliferative effects against multiple cancer cell lines. The primary anticancer mechanism identified was the induction of apoptosis, which is frequently mediated by the upregulation of p53 and Bax proteins, downregulation of Bcl-2, and induction of cell cycle arrest at the G1/S or G2/M phase. Flavonoids, particularly quercetin, have been identified as the key bioactive phytoconstituents that contribute to these effects. In vivo studies further support these findings, showing that D. pentandra extract can inhibit tumor progression in colitis-associated cancer models by reducing inflammatory markers such as myeloperoxidase (MPO).

Although routine treatment methods aim to aggressively destroy tumour tissues, they often fail to account for the correlations of tissue destruction and regeneration processes. Despite considerable progress in the field of oncology, it is worth noting the ancient ways of treatment using products from nature which potentially can effectively support current therapies.