Experimental Hematology & Oncology实验血液学与肿瘤学
Experimental Hematology & Oncology(英文缩写 EXP HEMATOL ONCOL),ISSN 2162-3619,eISSN 2162-3619,中文译名:实验血液学与肿瘤学 是一本学术期刊。本页汇总该期刊的最新影响因子、分区信息以及最新收录于 PubMed 的文献,帮助您快速了解期刊全貌。
发文量统计区间：2025-11-01 至 2026-10-31，按本站收录文献的发表日期统计。
期刊介绍
Experimental Hematology & Oncology 最新收录文献
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1. Targeting adaptive EGFR feedback enhances the therapeutic efficacy of RMC-6236 in cholangiocarcinoma.
PMID:日期:2026-10-03Approximately 20% of cholangiocarcinomas harbor KRAS mutations, with codon 12 variants accounting for most of the cases. Among these, G12V is associated with a poor prognosis, whereas G12D is the most frequent subtype. RMC-6236, a novel RAS (ON) multi-selective inhibitor targeting multiple KRAS codon 12 mutations, has shown promise in early clinical studies in KRAS-mutant cholangiocarcinomas. We evaluated the therapeutic efficacy of the novel RAS (ON) inhibitor RMC-6236 as a monotherapy and in combination with gemcitabine and the anti-EGFR antibody cetuximab in KRAS-mutant cholangiocarcinoma (CCA) models. Antitumor activity and signaling alterations were assessed using in vitro cell-based assays, western blot analysis, and in vivo xenograft models. RMC-6236 potently inhibited cell proliferation in KRAS-mutant (G12D and G12V) cell lines at nanomolar concentrations (10-30 nM) and effectively suppressed pERK signaling. Notably, RMC-6236 treatment was accompanied by increased pEGFR expression, indicating adaptive EGFR feedback activation as a potential mechanism of resistance. In vitro, combination treatments significantly enhanced growth inhibition compared with monotherapy. In xenograft models, RMC-6236 treatment induced dose-dependent tumor regression, whereas combination with cetuximab or gemcitabine further enhanced the antitumor efficacy. EGFR-mediated feedback represents a targetable vulnerability in KRAS-mutant cholangiocarcinomas. Targeting EGFR signaling attenuates adaptive feedback reactivation induced by pan-RAS (ON) inhibition and supports the clinical development of combination strategies with EGFR blockade or cytotoxic chemotherapy.
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2. Next-generation CAR-T therapy for malignant brain tumors: latest updates from the 2026 AACR Annual Meeting.
PMID:日期:2026-09-28The 2026 AACR Annual Meeting showcased rapid progress in chimeric antigen receptor (CAR) T-cell therapy for malignant brain tumors. This correspondence synthesizes 12 clinical and translational abstracts addressing early efficacy, resistance mechanisms, target discovery, and next-generation engineering. Phase I studies in glioblastoma demonstrated feasibility, manageable toxicity, cellular persistence, and preliminary radiographic activity, while revealing antigen loss and treatment-associated myeloid suppression. Longitudinal and spatial analyses further identified limited CAR T-cell persistence, anti-CAR immune responses, and remodeling of suppressive tumor niches. Preclinical strategies sought to overcome these barriers through programmable antigen recognition, alternative KIR/DAP12 signaling, stress-granule modulation, inducible metabolic support, membrane-tethered cytokine agonists, resistance to transforming growth factor beta, and dual targeting of tumor cells and immunosuppressive macrophages. Surfaceome profiling and affinity-guided receptor optimization also identified promising targets in glioblastoma and medulloblastoma. Collectively, these findings support mechanism-informed CAR T-cell platforms, while emphasizing that durability, neurotoxicity, trafficking, immunogenicity, and patient selection require validation in larger clinical studies.
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3. Daraxonrasib and the era of pan-RAS inhibition: mechanisms, clinical advances, and resistance landscapes.
3. Daraxonrasib与泛RAS抑制时代：机制、临床进展及耐药格局PMID:日期:2026-09-28Activating RAS mutations drive a substantial proportion of human cancers, yet for decades RAS was considered undruggable. The recent development of tri-complex inhibitors (TCIs) such as daraxonrasib (RMC-6236) has transformed the therapeutic landscape by enabling potent, multi-selective targeting of the active, GTP-bound state of multiple RAS isoforms. This review synthesizes preclinical and clinical evidence on daraxonrasib and related RAS(ON) inhibitors across RAS-mutant malignancies, including pancreatic ductal adenocarcinoma, non-small cell lung cancer, colorectal cancer, melanoma, and cholangiocarcinoma. We examine the structural basis of TCI action, pharmacokinetic considerations, and the profound tumor regressions observed in early-phase trials, including the unprecedented overall survival benefit in PDAC. A central focus is the emergence of resistance through diverse mechanisms: acquired mutations in CYPA, RAS, and BRAF that disrupt drug-target complex formation or restore RAS-RAF signaling; adaptive rewiring via mTORC1, STAT3, and cell cycle pathways; and tumor microenvironment-mediated resistance. We further explore rational combination strategies designed to forestall resistance, including vertical MAPK pathway blockade, orthogonal inhibition of EGFR/STAT3, CDK4/6 targeting, and immunotherapy combinations that leverage RAS inhibition-induced immune priming. By integrating structural biology, translational pharmacology, and clinical outcomes, this review provides a comprehensive framework for understanding the promise and challenges of pan-RAS inhibition in precision oncology.
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5. Combination of PARPi and topoisomerase I inhibitors is highly effective in olaparib-resistant ovarian cancer.
PMID:日期:2026-09-15High-grade serous ovarian carcinoma (HGSOC) often shows an initial response to poly (ADP-ribose) polymerase inhibitors (PARPi) such as olaparib, particularly in tumors with defects in homologous recombination (HR), but resistance to these drugs is a major clinical challenge. To address this, we screened over 1400 FDA-approved compounds to find agents that could restore olaparib sensitivity in resistant ovarian cancer cells. DNA topoisomerase I inhibitors (TOP1i) emerged as the most effective partner. The combination of TOP1 inhibitors with PARPi showed strong synergistic anticancer effects across multiple murine and human HGSOC models, regardless of HR status, including patient-derived xenografts made resistant to olaparib. The combination was well tolerated and primarily worked by inducing apoptosis and increased DNA damage. These findings suggest that TOP1 inhibitors combined with PARP inhibitors could be a promising treatment strategy for olaparib-resistant ovarian cancer.
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6. Dysregulated KMT2D mutant targeting immunogenic rewiring to overcome epigenetic entropy promotes follicular lymphomagenesis.
PMID:日期:2026-09-15Epigenetic modifier factors in B cell lymphomas often harbor loss-of-function mutations. Mutations occurring in the histone-lysine methyltransferase 2D (KMT2D) gene are the pivotal chromatin-modifying hallmarks of follicular lymphoma (FL) subsets, however their tumor-promoting roles are unclear. Targeted sequencing was employed to evaluate a core panel of genes implicated in histone methylation (EZH2, KMT2D), histone acetylation (CREBBP, EP300), and chromatin remodeling (ARID1A, BCL7A) in FL patients. Functional characterization of the KMT2D mutation (KMT2D) was carried out in vitro. RNA sequencing analysis was utilized to identify differentially expressed genes (DEGs) and significantly enriched pathways. The role of aldehyde dehydrogenase 1 family member A1 (ALDH1A1) in mediating the function of the KMT2D was investigated in B-lymphoma cell models using lentivirus. Through transcriptome deconvolution, integrative analyses combining chromatin immunoprecipitation and genome-wide chromatin accessibility were performed in KMT2D-mutant cell lines. Additionally, chromatin immunoprecipitation, immunofluorescence assays, and immunoblotting analyses were conducted. KMT2D mutations were the most frequent genetic alterations in FL (63%), predominantly consisting of nonsense and frameshift variants. Compared with wild-type, KMT2D-mutant FL exhibited markedly reduced H3K9me3 levels and increased chromatin accessibility at distal regulatory regions. Functionally, KMT2D promoted proliferation, suppressed apoptosis, and arrested cells in G2 phase. In FL, mutant KMT2D suppressed H3K9 methylation, leading to ALDH1A1 upregulation and the emergence of a highly plastic B‑cell state, followed by ATP7A overexpression, which ultimately reshaped the immune microenvironment. KMT2D drives FL progression by relieving H3K9me3-mediated epigenetic modification, activating PDK1/SGK1 signaling and an ALDH1A1-driven stemness program, and upregulating ATP7A to rewire copper homeostasis and redox balance. Our findings delineate a central molecular network through which KMT2D operates in FL and provide a mechanistic rationale for therapeutic targeting of KMT2D.
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7. Multimodal AI and single-cell transcriptomics integrate to construct a histopathological prognostic model for bladder cancer, revealing the RTN3-glycolysis axis in chemoresistance.
PMID:日期:2026-09-15Bladder cancer is a common malignant tumor of the urinary system, and gemcitabine-based chemotherapy often fails because of drug resistance. Tumor heterogeneity, particularly copy number variations (CNVs) heterogeneity at the genomic level, is a core factor that drives disease progression and drug resistance. However, the relationship between CNV heterogeneity at the single-cell level and the histomorphological features that are relied upon in a routine pathological diagnosis remains unclear, limiting its application in clinical prognostic assessments and precision therapy. This study integrated six public single-cell RNA sequencing (scRNA-seq) datasets as discovery cohorts to systematically analyze the cellular landscape of bladder cancer. The inferCNV algorithm was used to infer CNVs at the single-cell level and identify subpopulations with high CNV (HCNV). A multimodal artificial intelligence (AI) strategy combining deep learning and image analysis was employed to construct a prognostic model based on routine H&E-stained pathological sections, with HCNV activity serving as a biological anchor for pathology feature selection. Hub genes were screened using multiomics data, and in vitro and in vivo functional experiments using bladder cancer cell lines were conducted to validate the functions and mechanisms of these hub genes. The single-cell analysis revealed that HCNV cells constitute a malignant subpopulation with a unique molecular phenotype characterized by widespread activation of oncogenic pathways (such as TGF-β, JAK-STAT and PI3K), active communication with the tumor microenvironment (e.g., cancer-associated fibroblasts and M2 macrophages), and a poor prognosis for patients. The multimodal AI-based pathological imaging model effectively predicted patient survival. The model-derived risk score showed a significant but modest correlation with transcriptomic HCNV activity. Through multi-algorithm feature selection, we identified RTN3 as the core gene driving the HCNV phenotype. Our study confirms that RTN3 not only orchestrates an immunosuppressive microenvironment but also directly mediates resistance to gemcitabine. Mechanistically, RTN3 activates the JAK2/STAT3 signaling pathway, which transcriptionally upregulates key glycolytic enzymes (PKM2, GLUT1, and LDHA), thereby driving glycolytic metabolic reprogramming and ultimately conferring gemcitabine resistance in bladder tumors. This study reveals a malignant cell subtype defined by HCNV in bladder cancer at the single-cell level and elucidates the molecular and microenvironmental basis of the poor prognosis of bladder cancer. A clinically translatable multimodal AI pathological prediction model was successfully developed. Furthermore, our findings establish the RTN3/JAK2/STAT3/glycolysis axis as a critical mechanism of gemcitabine resistance, highlighting RTN3 as a promising therapeutic target for overcoming chemoresistance in bladder cancer.
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8. CD84 expression stratifies venetoclax response and reveals a targetable vulnerability in resistant acute myeloid leukemia.
PMID:日期:2026-09-07Venetoclax-based regimens have become increasingly integrated into the therapeutic landscape of acute myeloid leukemia (AML), yet primary resistance and relapses remain major barriers to durable benefits. Building on our previous discovery of CD84 as a critical survivor and redox regulator in AML, we here demonstrate that CD84 expression contributes to venetoclax sensitivity. Low CD84 expression is associated with favorable clinical response, whereas high CD84 expression correlates with primary resistance and is up-regulated at relapse in two of three paired samples. Functional perturbation of CD84 through genetic knockdown or CD84-targeted CAR-T cells sensitized AML cells to venetoclax in vitro and in vivo cell-derived xenograft models. Mechanistically, CD84 coordinates a pro-survival program with upregulating the antioxidant stress sensor SESN2, which suppresses mitochondrial reactive oxygen species and antagonizes venetoclax-induced apoptosis. SESN2 knockdown phenocopied CD84 depletion, while SESN2 overexpression partially restored venetoclax resistance in CD84-deficient cells. Our findings suggest that CD84-mediated upregulation of SESN2 contributes to venetoclax resistance and may represent a potential therapeutic target to enhance treatment efficacy in AML.
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9. {"_":"Tumor-intrinsic NSUN2 orchestrates immunosuppression in lung adenocarcinoma via the mC-HDAC8-CCL5 axis.","sup":["5"]}
PMID:日期:2026-09-07Insufficient T-cell infiltration is a major barrier to the efficacy of immune checkpoint inhibitors (ICIs) in lung adenocarcinoma (LUAD). We aimed to investigate how the tumor-intrinsic mC methyltransferase NSUN2 shapes the immune landscape of LUAD. Nsun2 conditional knockout mice and syngeneic mice models were employed. Single-cell RNA sequencing (scRNA-seq) and mC sequencing were performed to elucidate the downstream pathway regulated by NSUN2. LUAD specimens from patients receiving neoadjuvant immunotherapy were used to assess the correlation between NSUN2 expression and immune infiltration. Elevated tumoral NSUN2 expression was correlated with a marked lack of CD8 T-cell infiltration and immunotherapy resistance. Mechanistically, NSUN2 enhances the translation of histone deacetylase HDAC8 in an m⁵C-YBX1-dependent manner, which in turn directly represses the transcription of the chemoattractant CCL5, thereby impairing CD8 T-cell recruitment into the tumor. NSUN2 depletion reversed this immunosuppressive axis and converted immunologically "cold" tumors into "hot". Tumor-targeted liposomes loaded with the NSUN2 inhibitor synergized with anti-PD-1 therapy to induce significant tumor regression. Our findings identify NSUN2 as a critical orchestrator of T-cell exclusion in LUAD. It serves as both a candidate predictive biomarker for ICI failure and a promising druggable target. Targeting NSUN2 offers a potential strategy to overcome immunotherapy resistance and improve clinical outcomes in LUAD patients.
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10. Chimeric antigen receptor (CAR)-T cell therapy for solid tumors in pediatric patients: current breakthroughs, dilemmas, and strategies.
PMID:日期:2026-09-05Chimeric antigen receptor (CAR)-T cell therapy has demonstrated substantial clinical efficacy in pediatric hematologic malignancies; however, its application in pediatric solid tumors remains investigational and is constrained by substantial biological and clinical challenges. Key barriers comprise tumor heterogeneity, antigen escape, T-cell exhaustion, physical barriers and immunosuppressive tumor microenvironment, treatment-related toxicities, and pediatric-specific considerations, including optimal dosing and potential long-term developmental sequelae. Ongoing research focuses on identifying novel target antigens, optimizing CAR architectures, genetically engineering CAR-T cells, and improving delivery strategies to address these barriers. In this review, we summarize recent advances, persistent challenges, and emerging strategies for CAR-T cell therapy in pediatric solid tumors. We also discuss rational combination strategies involving CAR-T cell therapy with chemotherapy, radiotherapy, and immune checkpoint inhibitors aimed at improving therapeutic efficacy and safety. As the field continues to evolve, advances in CAR-T cell therapy may expand therapeutic options for pediatric solid tumors, although further clinical investigation is required to establish its long-term efficacy and safety.