Background and objectives Diffuse large B-cell lymphoma presents a significant challenge due to its high rate of treatment failure in 40% of patients. In this study we screened microRNAs as biomarkers in chemotherapy non-responding patients, to allow their early prognostication. Methods In the exploratory phase, whole transcriptome microRNA profiling was conducted on 10 diffuse large B-cell lymphoma cases. Three patients achieved complete remission, while seven had refractory or relapsed disease. The differentially expressed miRNAs were validated in 41 retrospective, treatment-naive diffuse large B-cell lymphoma biopsies, including the original 10 cases. Additionally, 33 cases with paired biopsy and plasma samples were prospectively evaluated using qRT-PCR to correlate miRNA expression with clinical outcomes. Functional validation to identify downstream pathways was done by knocking down identified miRNAs in JM-1 cells by semi-quantitative proteomics. Results miR-193b-5p, miR-1307-5p, and miR-671-5p expression were downregulated in refractory/relapsed diffuse large B-cell lymphoma biopsies. Plasma miRNA levels did not reflect prognosis. In vitro proteomics showed their impact on key oncogenic pathways, revealing significant enrichment of replication and transcription-related proteins. Interpretation and conclusions The expression of miR-193b-5p, miR-1307-5p, and miR-671-5p miRNAs in diffuse large B-cell lymphoma tissues may serve as predictive biomarkers.

Background and objectives Ovarian carcinoma is one of the most lethal carcinomas among females. Its high prevalence and shorter 5-year survival rate is due to the fact that most of the cases are diagnosed at later stages. This highlights the importance of early diagnosis through reliable biomarkers. We studied the diagnostic role of SOX9 protein in ovarian carcinoma and its diagnostic ability. The primary objective was to compare the level and clinical relevance of SOX9 protein in the tissues of patients with ovarian carcinoma with non-malignant ovarian tissues. Methods Tissue levels of SOX9 protein were estimated in the study and control groups (60 each group). SOX9 levels were compared between the study vs. control groups and also between high grade and low-grade ovarian cancer. SK-OV3 ovarian adenocarcinoma cell line was used as supportive evidence to prove the presence of SOX9 in malignant ovarian cells. Results Levels of SOX 9 protein (3.9±2.7 ng/mL) were high in tissue of ovarian cancer patients when compared to non-malignant (1.5 ±1.1 ng/mL) ovarian tissues. Higher levels of SOX 9 protein were found in tissues of ovarian cancer patients when compared to non-malignant ovarian tissues. The mean of SOX 9 levels in tissues of high-grade serous carcinoma was 3.5±2.5 ng/mL as compared to 1.0±0.9 ng/mL in low-grade serous carcinoma. Interpretation and conclusions SOX9 appears to be an important player in the molecular tumourigenesis of ovarian cancer, particularly in high grade tumours.

Background and objectives Genomic studies are essential for identifying mutations that may influence key aspects of breast tumours, such as susceptibility, aggressiveness, and response to treatment. There are deficient molecular and genomic data from Indian breast cancer patients. Methods mRNA from primary breast cancer samples were subjected to next-generation transcriptome (mRNA) sequencing on an Illumina platform, in duplicates and triplicates to generate 30-60 M reads/sample. PAM50, and absolute intrinsic molecular subtyping (AIMS) gene expression-based classifiers were used for intrinsic subtyping. Variants were called using, GATK, MuTect2, VarScan2, and VarDict, followed by filtering for somatic and non-synonymous changes. Germline variants were excluded using public databases. ClinVar annotations prioritised pathogenic variants, and the STRING algorithm was used for network analysis. Results A total of 207 RNA-Seq datasets from 97 breast cancer patients were analysed. There was good concordance between the immunohistochemical receptor and AIMS classification for all subtypes, but there was discordance between immunohistochemical and PAM50 subtypes within the ER-positive/HER2-positive subgroup, wherein only 38.5% (n= 5) were classified as HER2-like by gene expression classification. Variant analysis identified 145 high-confidence somatic mutations, with TP53 (n=46, 47%) and PIK3CA (n=33, 34%) being the most frequent. Additional actionable mutations in BRCA1, BRCA2, FGFR2, PTEN, AKT1, and mTOR pathways were identified. At least one actionable mutation was found in 52% of patients. Fusion transcript analysis identified 91 recurrent fusions, including novel partners with ERBB2, MED1, and CDK12, suggesting the possibility of unique molecular events. Interpretation and conclusions This study demonstrates that Indian breast cancer patients exhibit molecular subtypes and actionable mutations comparable to Caucasian cohorts.

BackgroundSERPINE1 has attracted considerable attention in tumor biology, but its clinical importance in head and neck squamous cell carcinoma (HNSCC) is not yet clear. We therefore examined whether SERPINE1 expression is related to survival in patients with HNSCC.MethodsWe searched three major databases (PubMed, EMBASE, and the Cochrane Library) and identified observational studies reporting survival outcomes in relation to SERPINE1 expression through November 11, 2024. From eligible reports we extracted data on progression-free survival (PFS), overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS), and calculated pooled hazard ratios (HRs) using random-effects models.ResultsEleven studies including 733 individuals with HNSCC met the inclusion criteria. Across these cohorts, higher SERPINE1 expression was consistently linked with shorter OS (HR 2.81, P = 0.003) and shorter DFS (HR 1.57, P = 0.004). In contrast, no clear associations were observed for PFS or DSS (P ≥ 0.05).ConclusionCurrent evidence suggests that increased SERPINE1 expression is associated with an unfavorable prognosis in HNSCC, particularly for OS and DFS. Larger prospective studies are needed to confirm these findings and to determine how SERPINE1 assessment might be incorporated into risk stratification and treatment planning for patients with HNSCC.

Histone modification is an important mechanism of epigenetic regulation. New histone modifications play key roles in the regulation of gene expression and in the development and progression of various diseases. In addition to histone modifications, epigenetic regulation includes classic pathways such as DNA methylation, chromatin remodeling complexes and non‑coding RNAs, which interact with each other and jointly shape the occurrence and development of gastric cancer (GC). The present study systematically elaborated on the role of histone modification in GC and introduced several main types of histone modification, including acetylation, methylation, citrullination, ubiquitination and lactylation, focusing on histone lactylation modification and exploring its biochemical basis, interaction with other modifications and functions such as metabolic reprogramming, cell proliferation, migration and immune escape, covering non‑tumor and other cancer fields. On this basis, the specific application of histone modification (acetylation, methylation and other modifications) in GC is further explained and the effects of histone lactylation on metabolic reprogramming, proliferation, migration and immune escape of GC are analyzed in detail. Finally, the clinical significance of histone lactylation modifications in the diagnosis and prognosis of GC, biomarkers, therapeutic targets and drug resistance mechanisms provides a reference for an in‑depth understanding of the role of histone modifications, especially lactylation modifications, in the development of GC and clinical transformation applications.

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.

-Synovial sarcoma is a rare soft tissue sarcoma. Treatment of synovial sarcoma includes surgery, radiation, pazopanib, and chemotherapy. Targeted therapies, such as B-Raf proto-oncogene, serine/threonine kinase (BRAF) inhibitors, are emerging as a potential treatment option. We describe the sixth case of a BRAFV600E synovial sarcoma, the first extra-thoracic case. This case is the first to show a complete pathological response to BRAF & mitogen-activated protein kinase kinase (MEK) inhibitors.

Malignant melanoma (MM) is a highly aggressive skin cancer known for its rapid progression, potential for metastasis, and resistance to treatment. Despite advances in targeted therapies and immunotherapy, the prognosis for metastatic melanoma remains unfavorable. Recent research has shed light on the significance of epigenetic modifications in the pathogenesis of melanoma, revealing critical mechanisms of melanoma development and progression. Epigenetic modifications, including DNA and RNA modifications, histone modifications, chromatin remodeling, and non-coding RNA regulation, disrupt normal gene expression without modifying the DNA sequence, leading to cellular transformation, invasion, immune evasion, and therapeutic resistance. The reversible nature of epigenetic modifications opens up new opportunities for melanoma recognition and classification, as well as therapeutic applications, including the development of diagnostic and prognostic biomarkers and innovative targeted therapies aimed at restoring normal gene function and enhancing the efficacy of existing treatments. This review will focus on the multifaceted role of epigenetic dysregulation in melanoma. The future integration of epigenetic data and genomic profiling with clinical outcomes, likely facilitated by artificial intelligence (AI) algorithms, holds promise for personalized treatment strategies that are informed by precise and combinatorial diagnostic tools, ultimately improving melanoma care. The study aims to deliver a comprehensive overview of the current state of epigenetics in melanoma.

An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer (SCLC). The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.

Protein arginine methyltransferases (PRMTs) catalyze the methylation of arginine residues on both histone and non-histone substrates, orchestrating cellular processes such as transcriptional regulation, RNA splicing, signal transduction, and DNA damage response. Because dysregulated methylation reprograms epigenetic and post-transcriptional landscapes to promote malignant transformation, aberrant PRMT activity is closely associated with tumorigenesis and cancer progression. Major family members, containing PRMT1, CARM1, PRMT5, and PRMT6, regulate gene expression through site-specific histone methylation, thereby contributing to the transcriptional activation or repression. PRMTs also methylate a wide range of non-histone proteins, including transcription factors, splicing regulators, and signaling intermediates, to coordinate cell cycle progression, DNA repair, and RNA metabolism. Collectively, PRMT-mediated methylation contributes to higher-order cancer phenotypes, including metabolic reprogramming-through modulation of glycolytic flux, lipid biosynthesis, and redox homeostasis-and immune evasion via altered immune signaling and checkpoint pathways within the tumor microenvironment. Recent advances in chemical biology have led to the development of selective PRMT inhibitors, several of which are currently under clinical evaluation. In this review, we provide a comprehensive and integrative overview of PRMT biology, systematically organizing current knowledge from multilayered regulatory mechanisms to downstream oncogenic effects and emerging therapeutic opportunities.

The Muscleblind-like (MBNL) family comprises evolutionarily conserved RNA-binding proteins that interact with target RNAs via zinc finger domains. MBNLs orchestrate RNA processing, particularly alternative splicing, driving the developmental fetal-to-adult isoform switch across numerous target transcripts. This transition is a cornerstone in the process of MBNL-maintained cellular homeostasis and fails in many pathological conditions associated with deregulated expression or function of specific MBNL paralogs. This review provides current insights into the roles of MBNL genes and proteins in both health and disease. We examine their genomic architecture and protein organization and synthesize key insights from animal models to delineate the selective and compensatory functions of individual MBNL paralogs in physiology. To illustrate the roles of MBNLs in disease, we outline nucleotide repeat expansion disorders marked by their functional depletion, with a primary focus on myotonic dystrophy (DM). We also highlight selected cancer studies that have demonstrated the dual roles of MBNLs in tumorigenesis, encompassing both pro-oncogenic and tumor suppressive functions. Finally, using DM as a model, we review evidence for the therapeutic potential of endogenous MBNL gene modulation and argue that analogous strategies could be adapted and tailored to restore MBNL homeostasis in other disorders involving their dysregulation.

The Hippo/YAP signaling pathway is a key regulatory network that governs organ size, tissue homeostasis, cell proliferation, and cell polarity. Aberrant Hippo/YAP signaling contributes to the initiation and progression of multiple cancers, making this pathway an attractive therapeutic target. Although several agents targeting Hippo/YAP have shown promise in preclinical models, clinical translation has been limited. These challenges likely stem from an incomplete understanding of the upstream regulators, downstream effectors, pathway crosstalk, and context-dependent roles of Hippo/YAP across different tumor types. Continued mechanistic investigation is required to clarify these complexities and reveal new therapeutic vulnerabilities. In this review, we summarize the current knowledge of the core components of the Hippo/YAP pathway, its regulatory mechanisms and interactions with other signaling cascades, its dysregulation in cancer, the involvement of microRNAs and lncRNAs in pathway modulation, and emerging therapeutic strategies targeting Hippo/YAP.

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.

Targeted therapies have significantly transformed the management of chronic lymphocytic leukaemia (CLL), yet most recommendations continue to reflect Western practice patterns. Variations in disease biology, healthcare resources and treatment accessibility across the Asia-Pacific (APAC) necessitate region-specific guidance. The Asia-Pacific Leukaemia Consortium (APLC) therefore developed updated consensus statements to support standardised, context-appropriate care for patients with CLL.

Clonorchis sinensis, a common food-borne liver fluke in East Asia, is a Group 1 carcinogen strongly linked to cholangiocarcinoma. In recent years, molecular biology and multi-omics studies have revealed that this parasite drives chronic inflammation of the bile duct epithelium, epigenetic abnormalities, and the formation of precancerous lesions. Concurrently, circulating miRNAs, DNA methylation patterns, differential protein expression, metabolite profiles, and parasite-specific antigens have been proposed as potential early molecular biomarkers, which offers new avenues for the non-invasive detection of precancerous conditions. However, current research mainly remains at the laboratory stage and studies have small-scale cohorts, lacking multi-center, large-sample prospective validation and standardized detection protocols, which limits their clinical applicability. Furthermore, traditional imaging and histological methods exhibit limited sensitivity for early identification. This review aims to systematically summarize the molecular carcinogenic mechanisms associated with C. sinensis infection, recent advances in molecular biomarker research, and strategies for identifying precancerous lesions. It will particularly focus on discussing the major obstacles in clinical translation and future directions, with the goal of providing insights for early screening and prevention strategies.

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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Metabolic reprogramming is a hallmark of cancer, with the Warburg effect-driven aerobic glycolysis leading to a substantial accumulation of lactate in the tumor microenvironment. For a long time, lactate was considered a mere metabolic end product; however, recent studies have found that it acts as an important signaling molecule, profoundly influencing tumor progression by inducing a novel post-translational modification - lactylation. Lactylation, driven by lactate, occurs on both histones and non-histone proteins and is finely regulated by the 'writer' 'eraser' and 'reader' mechanisms, thereby altering the function of target proteins and gene expression. This review systematically explores the bidirectional regulatory network between glycolytic reprogramming and lactylation: on one hand, key glycolytic regulators promote lactate production, thereby increasing lactylation levels; on the other hand, lactylation can feedback to regulate the activity and expression of key glycolytic enzymes, forming a pro-tumor positive feedback loop. This interaction plays a central role in tumor proliferation, metastasis, DNA damage repair, and immune evasion. Consequently, targeting lactate production, lactate transport, or the lactylation process itself has emerged as a highly promising anti-cancer strategy and shows potential synergy with existing therapies such as immune checkpoint inhibitors. In-depth analysis of the glycolysis-lactylation axis will provide a crucial theoretical basis for developing novel cancer treatment approaches.
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First-line immunotherapy for advanced non-small cell lung cancer (NSCLC) shows significant survival benefits in patients without driver mutations, but the optimal duration of treatment remains controversial. Some studies support limiting immunotherapy to 2 years, arguing that longer treatment does not bring additional survival benefits; while other studies believe that treatment should continue until disease progression to maximize survival benefits. This article systematically reviews the current research progress on the duration of immunotherapy and discusses the potential predictive value of biomarkers such as circulating tumor DNA (ctDNA), the best efficacy response, and programmed cell death ligand 1 (PD-L1) expression levels in individualized treatment decisions. More prospective studies, especially biomarker-driven trials, are still needed to clarify the optimal duration of treatment and establish an individualized treatment strategy based on multidimensional indicators.
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Circular RNAs (circRNAs) are covalently closed, single-stranded RNAs generated via backsplicing. They are highly stable and evolutionarily conserved, making them promising candidates for cancer therapy and diagnosis. CircRNAs regulate cancer progression by modulating genome instability, angiogenesis, metastasis, stemness, and chemoresistance. They do so through mechanisms including microRNA (miRNA) sponging, protein interaction, translational templating, and transcription/translation regulation. CircRNAs play a critical role in cancer immunotherapy. They modulate immune checkpoint blockade (ICB) responses and cytokine secretion to reshape the tumor immune microenvironment (TME). CircRNAs also serve as stable platforms for neoantigen-based cancer vaccines and improve in vivo chimeric antigen receptor T cell (CAR-T) therapy by replacing unstable linear mRNA. Additionally, circRNAs are potential noninvasive biomarkers due to their abundance in body fluids and differential tumor-normal expression. Despite challenges such as unclear regulatory networks, off-target effects, and inefficient delivery, this review systematically summarizes the biogenesis of circRNAs, their functional mechanisms, their roles in cancer progression, and their applications in cancer immunotherapy. The review also highlights their utility as biomarkers and future translational directions, providing a focused overview of their potential to advance cancer immunotherapy.

The incidence of cancer increases markedly with aging, and the two processes share underlying molecular mechanisms. In the context of global population aging and rising cancer incidence, nine convergent hallmark axes have been identified: genomic instability, epigenetic drift, inflammation-immunity imbalance, microbiome dysbiosis, metabolic reprogramming, telomere attrition, stem cell exhaustion, cellular senescence, and autophagy dysfunction. These hallmarks constitute an integrated regulatory network that operates synergistically, antagonistically, or through bidirectional feedback across molecular, cellular, and microenvironmental levels. Genomic instability, epigenetic remodeling, chronic inflammation, microbiome dysbiosis, and metabolic reprogramming in aging often act synergistically to promote tumorigenesis, whereas telomere attrition and stem cell exhaustion primarily exert antagonistic, tumor-suppressive effects. Cellular senescence and autophagy dysfunction display context-dependent dual roles. Importantly, this network framework has direct relevance to cancer therapeutics. Although chemotherapy, radiotherapy, and immunotherapy effectively suppress tumor progression, they frequently induce therapy-induced senescence, characterized by cell-cycle arrest and a senescence-associated secretory phenotype, thereby accelerating functional decline and increasing long-term toxicities in older patients. The proposed "synergistic-antagonistic-dual" framework linking aging and cancer not only helps explain the disproportionate cancer burden in older adults but also supports a "one drug, two targets" therapeutic paradigm. Targeting these shared pathways has delayed aging phenotypes and suppressed tumorigenesis in preclinical studies and early clinical trials, highlighting the potential of integrated interventions that concurrently address aging and cancer.