Hepatocellular carcinoma (HCC) lacks reliable prognostic biomarkers for immunotherapy. Immunogenic cell death (ICD) represents a promising therapeutic target, but its comprehensive characterization in HCC remains unexplored.

Acute myeloid leukemia (AML) remains a therapeutic challenge due to its high relapse rate and limited treatment options. This study aimed to identify and validate novel circulating protein biomarkers with causal roles in AML pathogenesis using an integrative multi-omics approach.

Breast cancer (BC) remains a widespread malignancy and ranks as the second leading cause of cancer-related mortality among women worldwide. Hypoxia, epithelial-mesenchymal transition (EMT), and immune-related processes have been increasingly recognized as critical contributors to BC pathogenesis. However, a prognostic model integrating hypoxia-, EMT-, and immune-related genes (HEMTIRGs) to predict BC outcomes has not yet been established.

The recent advancement of mRNA technology has opened new therapeutic avenues for treating hematologic malignancies, offering innovative approaches to enhance existing immunotherapies. This review examines the expanding role of in vitro transcribed (IVT)-mRNA-based platforms in hemato-oncology, focusing on key areas: monoclonal antibody production, bispecific antibody development, and CAR-T cell engineering. Unlike conventional biologics, mRNA allows for in vivo expression of therapeutic proteins, reducing manufacturing complexity and expanding access through scalable, cell-free synthesis. IVT-mRNA-encoded monoclonal and bispecific antibodies can overcome limitations such as short half-life and the need for continuous infusion, while enabling innovations like Fc silencing, protease-activated masking, and combinatorial immunotherapies. In CAR-T cell therapy, IVT-mRNA provides transient, safer alternatives to viral vector-based approaches and facilitates emerging strategies such as in vivo CAR programming and IVT-mRNA vaccine-like boosters. Despite these advantages, challenges remain, including delivery precision, durability of therapeutic effects, and limited clinical trial success. Beyond therapeutic mechanisms, the integration of bioinformatics and AI in IVT-mRNA design is accelerating the development of personalized and efficient cancer treatments. Overall, mRNA technology is redefining immunotherapy in hematology and holds the potential to broaden access to advanced treatments globally.

Prognostication in pediatric and young adult osteosarcoma is typically limited to metastatic status at diagnosis and tumor necrosis after chemotherapy. Despite a complex genomic landscape, few molecular biomarkers are used clinically. This study evaluates the prognostic relevance of MYC amplification and MYC protein expression.

To evaluate the efficacy, safety, and predictive biomarker of a third-generation tyrosine kinase inhibitor (3G-TKI; ponatinib or olverembatinib) combined with azacitidine in chronic myeloid leukemia (CML) in myeloid blast phase.

The relapse after chimeric antigen receptor (CAR) T-cell therapy remains a critical challenge, and the optimal timing and treatment strategies for CAR T urgently need to be explored. Autologous hematopoietic stem cell transplantation (auto-HSCT) demonstrates comparable leukemia-free survival (LFS) and overall survival (OS) in patients who rapidly achieve MRD-negative complete remission (CR) compared with allogeneic HSCT (allo-HSCT). Thus, combining CAR T cells with auto-HSCT may represent a promising treatment strategy. The trial registration is ClinicalTrials.gov identifier NCT05470777.

Chromatin regulators (CRs) play a critical role in tumorigenesis, drug response, and prognosis, with dysregulation of chromatin regulator genes (CRGs) potentially disrupting the tumor immune microenvironment (TME) and influencing immune responses in cervical cancer. However, the prognostic and therapeutic implications of integrating CRGs and TME parameters in cervical cancer remain poorly understood.

GLI1 gene alterations including fusions and amplifications compromise a subset of malignant mesenchymal tumors exhibiting characteristic monomorphic nested morphology and frequent S100 positivity, which mimic glomus tumors or well differentiated neuroendocrine tumors. We report four high-grade uterine endometrial stromal sarcomas (ESS) harboring GLI1 and MDM2/CDK4 co-amplifications with a median age of 51.5 years (range 43 ~ 72 years). Histologically, tumors showed a heterogenous morphology, including ovoid to spindle cells, showing nested/nodular arrangement (4/4). Myxoid background was observed at least partially in 4 tumors with prominent capillary networks. Mitoses index was 2 to 20/10 HPF (median 9.5/10 HPF). Immunochemically, tumors showed diffuse staining of CD10 (3/4) with frequently positive CyclinD1(2/4 tested) and mostly negative S100 protein (3/4). Next-generationsequencing (NGS) studies revealed GLI1 and MDM2/CDK4 co-amplification in all cases (4/4) and GLI1 fusion in 1 case (1/4), which were validated by fluorescence in situ hybridization (FISH) analysis. BCOR fusions were firstly identified with GLI1 and MDM2/CDK4 co-amplification in 2 cases (2/4). Copy number (CN) segmentation data showed GLI1 co-amplified cases present generally a single peak at the 12q13.3-15 locus. Follow-up (range:3 to 112 months; median 37.5 months) showed recurrence and/or metastasis in all cases (4/4), in which 1 patient developed lungs and liver metastasis. Relapse-free survival (RFS) analysis showed similar median RFS between GLI1 co-amplified HGESS and GLI1 non-amplified HGESS groups, which were shorter than LGESS group. Unusual clinicopathologic features of these HGESS with GLI1 and MDM2/CDK4 co-amplification mimicked other neoplasms, which caused significant diagnostic challenge and pitfalls. However, identification of GLI1 alterations in these tumors is beneficial for diagnosis and potential use of targeted GLI1 inhibitors.

Long non-coding RNAs (lncRNA) H19 has drawn special attention because of its varied role in several malignancies, including OSCC. Therefore, this study was conducted to assess the association between H19-miR675-p53 by in-silico analysis, quantify the expression levels of H19, miRNA-675, and target oncogene p53 in cancerous versus normal individuals, and Correlate the Clinicopathological findings with their expression pattern.

Investigating the expression levels of immune checkpoint genes CD276, CD40, TNFSF14, and TNFSF9 in glioblastoma multiforme patients about copper death and patient prognosis.

Multiple myeloma (MM) is a major hematologic malignancy with limited therapeutic progress in radiotherapy. Although radiotherapy is widely used for palliation, its molecular effects in MM remain poorly defined. This study identifies RPL29 as a novel radiotherapy-responsive gene in MM and evaluates its prognostic and therapeutic relevance.

Spatial transcriptomics have emerged as a powerful tool in biomedical research because of its ability to capture both the spatial contexts and abundance of the complete RNA transcript profile in organs of interest. However, limitations of the technology such as the relatively low resolution and comparatively insufficient sequencing depth make it difficult to reliably extract real biological signals from these data. To alleviate this challenge, we propose a novel transfer learning framework, referred to as TransST, to adaptively leverage the cell-labeled information from external sources in inferring cell-level heterogeneity of a target spatial transcriptomics data.

Gefitinib is a first-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) used in the treatment of non-small cell lung cancer (NSCLC). It is metabolized extensively in the liver by enzymes encoded by CYP3A4, CYP2D6, and CYP3A5 and is the substrate of membrane transporters including ABCB1 and ABCG2. Evidence shows that single-nucleotide polymorphisms (SNPs) in these metabolizing and transporting genes contribute to the inter-individual variability in gefitinib response and development of gefitinib-induced adverse drug reactions (ADRs). This narrative review identifies the existing literature exploring the impact of SNPs on plasma gefitinib concentration and ADRs in patients with NSCLC receiving gefitinib therapy. SNPs were identified in drug-metabolizing enzyme coding genes, including CYP3A4, CYP2D6, CYP3A5, and other CYP homologs, drug transporters including ABCB1, ABCG2, SLCO1B1 and other genes, including UGT1A7 and FOXO3. Current research has not identified any genetic association between specific SNPs in ABCB1, OATP1B1, and UGT1A7 and the pharmacokinetics of gefitinib. Additionally, most of these studies focused on individual SNP associations; however, it may be more important to consider them in combination to better understand their collective impact on gefitinib ADR. Hence, further comprehensive research is essential to examine these genetic variants across different ethnic groups, monitor the drug-drug interactions, and study the phenoconversion to draw definitive conclusions about the pharmacokinetics of gefitinib. This could lead to the development and implementation of a genotyping-based approach for gefitinib dosage optimization in clinical settings.

Metastatic melanoma, the most aggressive form of skin cancer, accounts for the majority of skin cancer-related deaths. While targeted kinase inhibitors have improved outcomes for patients with BRAF-mutated melanomas, their efficacy is often short-lived, and effective treatments for other mutations, such as NRAS, remain scarce. To address this clinical need, we investigated the combination of the novel panRAF inhibitor, brimarafenib, and the MEK inhibitor, mirdametinib, both of which target the MAPK pathway downstream of NRAS. This study demonstrates the efficacy of this combination in NRAS-mutated melanoma and is currently also investigated in a phase I/IIa clinical study. In vitro, the brimarafenib and mirdametinib combination exhibited synergistic effects, significantly inhibiting the growth of patient-derived NRAS-mutated melanoma cell lines. A colony formation assay showed that this combination prevented the emergence of drug-resistant clones, suggesting a strong potential to reduce disease relapse. Transcriptional and proteomic analyses revealed that the observed growth inhibition was due to modulation of MAPK signaling and induction of apoptosis. In vivo studies further validated these findings, showing that the combination treatment inhibited tumor growth and significantly prolonged survival in mouse models bearing patient-derived NRAS-mutated melanoma tumors. Given the tolerability of this combination in vivo, our results suggest that brimarafenib and mirdametinib represent a promising therapeutic strategy for patients with NRAS-mutated melanomas and potentially other RAS-mutated solid tumors.

The molecular and functional changes in endothelial cells during disease progression such as cancer have been noted but the mechanism of their activation is still under-studied. Previously we discovered that tumor-derived Oncostatin M induced tumor-associated vascular phenotypes, and the activated endothelial cells in turn promoted tumor progression and metastasis of clear-cell renal cell carcinoma (ccRCC). However, the mechanism of Oncostatin M action remains unknown. Here, we reveal that Oncostatin M signaling triggers specific epigenetic reprogramming of endothelial cells through upregulation of lysine acetyltransferase 6B, leading to increased histone 3 lysine 14 acetylation (H3K14ac) in vitro and in vivo. H3K14ac-modified chromatins upregulate specific gene sets associated with hypoxic response, hyper-angiogenesis, inflammation, and mesenchymal transition. Targeting H3K14ac in endothelial cells by interfering with acetyltransferase 6B function or neutralizing Oncostatin M ameliorates the premalignant hyperplastic phenotypes in the autochthonous ccRCC mouse model and diminishes tumor growth and metastasis in the ccRCC xenograft model.

The combination of lazertinib and amivantamab has shown superior efficacy over first line osimertinib in EGFR-mutated metastatic non-small cell lung cancer, but is associated with significant toxicity and high costs. Lazertinib exposure varies widely due to genetic polymorphisms of the encoding for GSTM1, with almost 50% of Caucasians having a non-functional enzyme resulting in an approximate twofold higher systemic drug exposure. Despite this, all patients receive a fixed 240 mg once-daily dose irrespective of GSTM1 status, leading to avoidable toxicity without additional clinical benefit. Our purpose was to develop alternative dosing regimens based on GSTM1 status.

Ovarian cancer represents one of the most prevalent gynecological malignancies with a poor prognosis. Targeting glycolytic pathways has emerged as a novel cancer therapeutic strategy. N-acetyltransferase 10 (NAT10)-mediated N4-acetylcytidine (ac4C) modification plays a regulatory role in cancer glycolysis. Phosphoglycerate mutase 1 (PGAM1) functions as a critical glycolytic enzyme and potential therapeutic target in oncology. This study investigated the functional role and underlying mechanisms of NAT10 in ovarian cancer progression. Cellular glycolysis was assessed through glucose uptake measurements, lactate production quantification, and extracellular acidification rate analysis. Cell stemness characteristics were evaluated using sphere formation assays and western blot analysis. Molecular mechanisms were explored via quantitative real-time PCR, RNA immunoprecipitation (RIP), ac4C-specific RIP, dot blot analysis, and dual-luciferase reporter assays. Elevated NAT10 expression and ac4C modification levels were observed in ovarian cancer cells. NAT10 silencing significantly inhibited both cell stemness properties and glycolytic activity. Mechanistically, NAT10 enhanced PGAM1 mRNA stability through ac4C modification. Re-expression of PGAM1 reversed the functional effects induced by NAT10 depletion in ovarian cancer cells. Furthermore, in vivo tumor growth experiments demonstrated that NAT10 promotes tumorigenesis. Our findings demonstrate that NAT10 facilitates ovarian cancer progression by mediating ac4C modification of PGAM1. This study identifies a novel and potentially effective therapeutic target for ovarian cancer treatment.

Pancreatitis, or inflammation of the pancreas, is a common gastrointestinal condition. While often acute and self-resolving, it can become chronic and promote pancreatic ductal adenocarcinoma (PDAC), the third deadliest cancer worldwide. Pancreatitis is accompanied by morphological and molecular changes, notably immune cell infiltration, fibrosis, and acinar-to-ductal metaplasia (ADM). ELP3, the catalytic subunit of the Elongator complex, modifies wobble uridine tRNAs to optimize codon translation rates. It is critical to inflammatory processes and cancer in multiple organ systems, yet its role in the pancreas has not been investigated. This study aimed to investigate the expression and implication of ELP3 during pancreatitis induced in mice via repetitive caerulein injections. Acute pancreatitis was accompanied by increased expression of ELP3, which was mainly detected in pancreatic epithelial cells. To assess its function, we genetically inactivated Elp3 in pancreatic epithelial cells. Elp3 deficiency had no detectable effects on pancreas homeostasis, on the initiation and resolution of acute pancreatitis, on the development of chronic pancreatitis, or on pancreatitis-induced PDAC initiation. Our findings indicate that ELP3 is dispensable in pancreatic formation, inflammation and PDAC initiation. Future studies should explore its role in non-epithelial cells and its potential involvement in other PDAC hallmarks, such as therapy resistance.

Bladder cancer (BLCA) exhibits considerable heterogeneity, and research into its tumor microenvironment and prognostic biomarkers remains insufficient. This study aims to identify key prognostic genes and immune microenvironment factors to enhance clinical assessment. Primary tumor (PT) and lymph node metastasis (LNM) samples were obtained from patients with BLCA, and single-cell RNA sequencing (scRNA-seq) was conducted to analyze cellular composition and functional variations. Prognostic genes were identified based on integrated bulk transcriptomic data, leading to the development of a risk model. Functional enrichment analyses further elucidated the molecular characteristics of high- and low-risk cohorts. The scRNA-seq analysis revealed significantly elevated metabolic activity in epithelial cells of LNM. A subpopulation of epithelial cells, defined by 133 characteristic genes, was identified as pivotal in the lymphatic metastasis of BLCA. The prognostic model, derived from nine key genes (APOL1, CAST, DSTN, SPINK1, JUN, S100A10, SPTBN1, HES1, and CD2AP), demonstrated robust predictive performance. Functional enrichment analysis indicated that the high-risk group predominantly activated extracellular matrix (ECM) receptor interactions and the complement pathway, while the low-risk group was primarily associated with carbohydrate metabolism pathways. This study provides insights into the tumor heterogeneity and immune microenvironment of BLCA, introduces a high-precision prognostic model, and establishes a novel theoretical basis for personalized BLCA treatment.