Clinical & Translational Oncology[JOURNAL]
Sun
200 papers
Corrigendum to "Clinical significance and molecular mechanism of CDX2-CBX3 regulatory axis in lung adenocarcinoma progression" [Transl Oncol. 2025 Nov 10:63:102590].
Liu S, Zhao Q, Ren D … +3 more , Kong L, Zhao H, Duan G
Transl Oncol · 2026 Feb · PMID 41539742 · Full text
Abstract loading — click title to view on PubMed.
Corrigendum to "A Clinical Study on the Efficacy of Concurrent Chemoradiotherapy Combined with Targeted Therapy and Hyperthermia in Patients with Locally Advanced Cervical Cancer" [Translational Oncology,Volume61, November 2025, 102516].
Jia Y, Zhang F, Zou K … +1 more , Zou L
Transl Oncol · 2026 Feb · PMID 41539741 · Full text
Abstract loading — click title to view on PubMed.
NEIL1 suppresses ROS accumulation to promote temozolomide resistance and malignant progression in glioma cells.
Li S, Fang C, Yuan Q … +1 more , Chen X
Transl Oncol · 2026 Mar · PMID 41534309 · Full text
BACKGROUND: Glioma is the most common malignant primary brain tumor. Temozolomide (TMZ) is the standard first-line chemotherapy, but its efficacy is severely limited by acquired resistance. Understanding resistance mecha...
BACKGROUND: Glioma is the most common malignant primary brain tumor. Temozolomide (TMZ) is the standard first-line chemotherapy, but its efficacy is severely limited by acquired resistance. Understanding resistance mechanisms, especially beyond traditional DNA repair, is crucial for improving outcomes. METHODS: We integrated multi-database glioma transcriptomics (TCGA, GTEx, CGGA). Bioinformatics (differential expression, WGCNA, glycolipid metabolism gene screening) and machine learning (LASSO, random forest) identified key genes, focusing on the DNA glycosylase NEIL1. Its expression was assessed in U251 MG cells versus TMZ-resistant (U251 MG/TMZ) cells. Gain/loss-of-function studies (lentiviral knockdown/overexpression) and pharmacological inhibition (a 2-thioxanthine derivative, TX16) were used to evaluate NEIL1's role in proliferation (CCK-8, EdU), migration, invasion, apoptosis (TUNEL), ROS, and TMZ sensitivity (IC50). A subcutaneous nude mouse model provided in vivo validation. RESULTS: NEIL1 was aberrantly expressed in glioma and enriched in PI3K-Akt/cAMP signaling, suggesting that it may promote the malignant behavior of U251 MG cells through these pathways. Its expression was significantly higher in TMZ-resistant cells (P < 0.001). NEIL1 overexpression promoted malignant phenotypes (proliferation, migration, invasion, P < 0.05), while its knockdown suppressed them. Critically, NEIL1 overexpression attenuated TMZ-induced ROS and DNA damage, increased cell viability and IC (1.2-fold), and bolstered TMZ resistance. The NEIL1 inhibitor TX16 reversed these malignant behaviors and restored TMZ sensitivity (P < 0.05), reinstating ROS-driven apoptosis. In vivo, NEIL1 promoted tumor growth, which was suppressed by TX16. CONCLUSION: NEIL1 drives glioma malignancy and TMZ resistance by mitigating oxidative stress and DNA damage, highlighting its role as a promising target to overcome chemoresistance.
Spatial and single-cell multi-omics reveal pro-angiogenic THY1⁺ fibroblast subtypes predicting prognosis in prostate cancer.
Huang Y, Xiang C, Wang Y … +5 more , Zhang W, Du L, Wang W, Shi G, Wang J
Transl Oncol · 2026 Mar · PMID 41529384 · Full text
BACKGROUND: Cancer-associated fibroblasts (CAFs) play a key role in prostate cancer (PCa) progression, though their heterogeneity and specific protumorigenic subsets remain poorly characterized. This study aimed to ident...
BACKGROUND: Cancer-associated fibroblasts (CAFs) play a key role in prostate cancer (PCa) progression, though their heterogeneity and specific protumorigenic subsets remain poorly characterized. This study aimed to identify and validate a distinct THY1⁺ CAF subset associated with aggressive PCa. METHODS: Multiomics data from public (TCGA-PRAD, GEO) and prospective (FUSCC, n = 84) cohorts were analyzed. An 8-gene CAF-derived prognostic signature was constructed using LASSO Cox regression. THY1⁺ CAF clusters were identified via scRNA-seq. Primary CAFs were isolated from patient tissues, and THY1⁺/THY1⁻ subpopulations were purified via MACS/FACS. Angiogenic function and secretory profiles were assessed through tube formation assays, ELISA, and antibody arrays. THY1 knockdown and CXCR2 inhibition were used for mechanistic studies. Clinical relevance was evaluated via qPCR and multiplex immunohistochemistry on tissue microarrays. RESULTS: High CAF abundance correlated with aggressive clinicopathological features and poor prognosis in PCa. The 8-gene signature effectively predicted biochemical recurrence (BCR). scRNA-seq revealed THY1⁺ CAFs as a proangiogenic subpopulation. THY1⁺ CAFs enhanced angiogenesis via increased secretion of CXCL6 and VEGFA. CXCL6 promoted endothelial tube formation through CXCR2 activation, while THY1 knockdown downregulated VEGFA and impaired angiogenesis. High THY1⁺ CAF infiltration was associated with significantly worse recurrence-free survival. CONCLUSION: THY1⁺ CAFs represent a proangiogenic subset that drives PCa progression via the CXCL6/CXCR2 axis and THY1-mediated VEGFA expression. These findings highlight stromal THY1 and the CXCL6/CXCR2 pathway as potential therapeutic targets.
Advances on drug therapy for KRAS-mutant non-small-cell lung cancer.
Tian T, Li W
Transl Oncol · 2026 Mar · PMID 41529383 · Full text
Lung cancer has an extremely high mortality rate among malignant tumors, posing a significant threat to human health Among all lung cancer cases, non-small cell lung cancer (NSCLC) accounts for a significant proportion a...
Lung cancer has an extremely high mortality rate among malignant tumors, posing a significant threat to human health Among all lung cancer cases, non-small cell lung cancer (NSCLC) accounts for a significant proportion and has become a hot topic in clinical research and treatment. The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most common oncogenic drivers in NSCLC, closely associated with tumor initiation, treatment response, and prognosis. However, due to the relatively smooth surface of the KRAS protein and the lack of drug-binding pockets, it has long been regarded as an "undrugable target". With further research, recently, targeted drugs targeting the KRAS gene mutation have achieved significant breakthroughs in clinical trials, especially the application of KRAS-specific inhibitors adagrasib and sotorasib, which has changed the treatment landscape for NSCLC patients. To address challenges such as tumor heterogeneity, the complexity of the tumor microenvironment, interpatient variability, and acquired drug resistance mechanisms, combination therapy strategies involving KRAS inhibitors have emerged sequentially. This article systematically reviews the progress of targeted therapy for KRAS-mutant NSCLC and the results of related clinical trials, while exploring novel therapeutic strategies for patients with KRAS mutations, aiming to provide a reference for the selection of clinical treatment regimens.
CTSB-positive tumor-associated macrophages shape prognosis and therapeutic response in lung adenocarcinoma.
Zhu C, Liang L, Xue N … +5 more , Mei D, Tian M, Zhang Z, Sun X, Ding X
Transl Oncol · 2026 Mar · PMID 41520491 · Full text
BACKGROUND: Lung adenocarcinoma (LUAD) remains a major clinical challenge in assessment of clinical outcomes and therapeutic response. Although tumor-associated macrophages (TAMs) are known as crucial regulators of tumor...
BACKGROUND: Lung adenocarcinoma (LUAD) remains a major clinical challenge in assessment of clinical outcomes and therapeutic response. Although tumor-associated macrophages (TAMs) are known as crucial regulators of tumor progression, their heterogeneity and prognostic relevance in LUAD have not been fully elucidated. METHODS: The heterogeneity of TAMs was detected by integration analyses of single-cell data and spatial transcriptome data. The CTSB TAM-related signature (CTRS) was developed by machine learning algorithms across four LUAD datasets. Multi-omics analysis and functional experiments were applied to uncover the potential role and mechanism of CTSB TAMs in LUAD. RESULTS: Single-cell analysis identified CTSB⁺ TAM as a crucial player in LUAD progression with poor prognosis. The spatial co-localization of CTSB⁺ TAMs and tumor cells was confirmed on LUAD slides. Our proposed CTRS was generated and validated in four independent LUAD cohorts, with high scores indicating unfavorable outcomes Furthermore, high CTRS scores were correlated with immunosuppressive status, and poor responses to immune checkpoint blockade. Functional experiments demonstrated the role of CTSB TAMs in boosting proliferation and migration in LUAD cells. CONCLUSION: Our research develops CTRS with reliable performance in evaluating patient clinical outcomes in LUAD, highlighting its potential utility in clinical decision-making.
Mechanistic and translational insights into plant-derived natural products in preclinical multiple myeloma research: Current evidence.
Li L, Xu J, Yu L … +5 more , Shi J, Li C, Gu J, Wang Y, Cui S
Transl Oncol · 2026 Feb · PMID 41512703 · Full text
Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of abnormal plasma cells, with marked heterogeneity and therapeutic refractoriness. Despite the introduction of proteasome inh...
Multiple myeloma (MM) is a hematological malignancy characterized by the clonal proliferation of abnormal plasma cells, with marked heterogeneity and therapeutic refractoriness. Despite the introduction of proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs), and chimeric antigen receptor T-cell (CAR-T) therapy, relapse and drug resistance remain major challenges that urgently need to be addressed. Plant-derived natural products have attracted increasing attention in recent years due to their multi-target synergistic effects, demonstrating unique potential in inducing MM cell apoptosis, reversing drug resistance, and modulating the immune microenvironment-making them a rising focus in translational medicine research. In this structured narrative review, we systematically summarize the anti-myeloma mechanisms of fourteen plant-derived natural products, including plant-derived monomeric compounds (baicalein, artemisinin, curcumin, celastrol, gambogic acid, resveratrol, ginsenosides, icariin, oridonin, plumbagin, formononetin) and standardized plant extracts (Strychnos nux-vomica root extract, dandelion flavonoids, Hedyotis diffusa polysaccharides). This review highlights their multi-target regulatory effects on signaling pathways, cell cycle modulation, and immune regulation, and further discusses their potential translational value in overcoming drug resistance and optimizing combination treatment strategies. Literature was retrieved from PubMed, Web of Science, and CNKI databases, covering studies published up to January 2025. Although plant-derived natural products exhibit promising multi-target regulatory mechanisms in MM therapy, their clinical translation remains limited by poor bioavailability of single compounds and the lack of standardized extracts. Future research should integrate systems pharmacology with clinical studies to elucidate multi-component synergistic networks and develop novel targeted formulations, thereby accelerating the efficient translation of phytochemicals from bench to bedside.
CAR-T therapy in non-small cell lung cancer: Clinical prospects, potential, and strategies for cardiotoxicity management.
Liu Y, Gao Y, Huo C … +4 more , Zeng T, Meng W, Zhang H, He Q
Transl Oncol · 2026 Feb · PMID 41496418 · Full text
Lung cancer ranks first among all malignancies in incidence, with current treatment strategies including surgery, chemotherapy, immunotherapy, and targeted therapy. Despite these advances, drug resistance in advanced non...
Lung cancer ranks first among all malignancies in incidence, with current treatment strategies including surgery, chemotherapy, immunotherapy, and targeted therapy. Despite these advances, drug resistance in advanced non-small cell lung cancer (NSCLC) remains a major obstacle and innovative therapeutic approaches are imperative to address it. Chimeric antigen receptor T-cell (CAR-T) therapy has shown impressive and long-lasting results in blood cancers, but its success in solid tumors such as lung cancer remains limited. This review summarizes recent advances and future directions of CAR-T therapy in NSCLC, focusing on major therapeutic targets such as EGFR, MSLN, PD-L1, MUC1, CEA, and ROR1, as well as on the efficacy and potential of combining CAR-T therapy with other treatment modalities. Additionally, we discuss adverse events in NSCLC patients undergoing CAR-T therapy, emphasizing cytokine release syndrome (CRS) and cardiovascular complications-their incidence, pathophysiology, interrelation, and management strategies.
Adaptive therapy for perioperative non-small cell lung cancer: strategies guided by dynamic minimal residual disease adjustment.
Xie LJ, Fu LL, Liu SC … +6 more , Bai CS, Xu BC, He XW, Lin HF, Zeng YC, Tang WJ
Transl Oncol · 2026 Feb · PMID 41496417 · Full text
Lung cancer remains the leading cause of cancer incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for about 85% of cases. The low rate of early diagnosis and the high rate of occult me...
Lung cancer remains the leading cause of cancer incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for about 85% of cases. The low rate of early diagnosis and the high rate of occult metastases limit the survival benefits of conventional treatments. The current TNM staging system fails to fully reflect tumor heterogeneity or the dynamic molecular evolution of the disease, thus affecting the prediction of recurrence and the prognostic stratification. Some recent advances in minimal residual disease (MRD) detection, such as ultra-sensitive liquid biopsy technologies, have largely overcome the limitations of traditional imaging and offered a transformative approach for continuous, precision-based management of lung cancer. This review systematically summarized the technological evolution of MRD detection and highlighted its clinical significance in guiding adaptive therapy for NSCLC, including treatment escalation, de-escalation, and the emerging concept of precision-guided drug holidays. Moreover, the authors comprehensively discussed the "Four-Dimensional TNMB Staging System," which incorporates continuous molecular monitoring to address the static limitations of conventional staging and enhance the accuracy of prognostic stratification. Although ongoing challenges, such as the lack of standardized interpretation criteria and limited detection sensitivity, the combinations with the third-generation liquid biopsy platforms, multi-omics analyses, and multi-center prospective validation studies are expected to advance the clinical implementation of MRD-guided strategies. The paradigm change will enable the transition of NSCLC management from conventional standardized models to a precision-guided, closed-loop system of "monitoring-intervention-remonitoring," establishing a solid theoretical and practical foundation for comprehensive, molecularly driven management strategies.
A serum-derived 3D tumor model platform for personalized prediction and monitoring of chemotherapeutic response in pancreatic ductal adenocarcinoma.
Cherradi S, Roux S, Dupuy M … +2 more , Assenat E, Duong HT
Transl Oncol · 2026 Feb · PMID 41496416 · Full text
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer, largely due to late diagnosis, tumor heterogeneity, and a dense, immunosuppressive stroma that limits therapeutic efficacy. While regimens like FOLF...
Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal cancer, largely due to late diagnosis, tumor heterogeneity, and a dense, immunosuppressive stroma that limits therapeutic efficacy. While regimens like FOLFIRINOX and gemcitabine-based therapies offer some benefit, treatment selection remains empirical, with no reliable predictive models to guide personalized decisions. We adapted our previously validated serum-derived educated spheroid technology creating 3D spheroids using PDAC patient serum. These spheroids maintained structural integrity, viability, and consistent size over eight days, avoiding overgrowth. They also exhibited extracellular matrix deposition such as type I collagen, and expressed key genes involved in drug resistance and tumor progression including COL1A1, FN1, MMP2, CXCL1, and CXCL2. Using the Target-Independent Cell Killing (TICK) strategy, we established individualized chemograms to assess true therapeutic response helping clinicians in refining the optimal treatment protocol. In a 16-case study, our model achieved high concordance with clinical responses across gemcitabine, Gem-Pac, and FOLFIRINOX treatments supporting its utility in personalized care. Finally, we demonstrated that predictive accuracy was highest when patient serum was collected within a short window prior to treatment initiation. These findings support PDAC patient serum-educated spheroids as a rapid, non-invasive, and physiologically relevant tool for guiding personalized chemotherapy and monitoring treatment response in real time.
Single‑cell mapping of neutrophil extracellular trap signatures in lung adenocarcinoma reveals immune landscapes, prognostic potential, and therapeutic targets.
Liu J, Tian K, Shen H … +4 more , Zhou L, Dong S, Huo F, Zhang J
Transl Oncol · 2026 Feb · PMID 41496413 · Full text
Neutrophil extracellular traps (NETs) have emerged as key modulators in the tumor microenvironment, yet their cellular heterogeneity, molecular mechanisms, and clinical relevance in lung adenocarcinoma (LUAD) remain elus...
Neutrophil extracellular traps (NETs) have emerged as key modulators in the tumor microenvironment, yet their cellular heterogeneity, molecular mechanisms, and clinical relevance in lung adenocarcinoma (LUAD) remain elusive. Here, we performed an integrative single‑cell and multi‑omics dissection of NETs activity across LUAD tissues. Single‑cell transcriptomics revealed that NETs signatures were predominantly enriched in neutrophils but also detectable in dendritic cells and macrophages, where NETs‑high subpopulations exhibited intensified intercellular signaling. Genomic profiling indicated that NETs‑related genes were largely affected by missense mutations and single nucleotide polymorphisms (C > A and C > T), with frequent alterations in PTPRD, VCAN, and ZNF804A. Functional enrichment associated these genes with immune regulation and tumor‑promoting pathways. By integrating seven independent clinical cohorts, we constructed a machine‑learning-based NETs‑related prognostic signature (NETs‑Sig) that robustly predicted overall survival across datasets (AUC > 0.75). Patients with high NETs‑Sig scores exhibited immune‑cold phenotypes characterized by reduced immune infiltration and impaired antigen presentation, whereas low‑score cases displayed elevated MHC‑II expression, enhanced antigen processing, and putative sensitivity to immunotherapy. Experimental validation further identified AP2S1 as a central NETs‑Sig gene-overexpressed in multiple cancers and functionally promoting invasion and metastasis in LUAD cells. Together, our study delineates the cellular, genomic, and immunological frameworks of NETs in LUAD, establishes NETs‑Sig as a clinically actionable biomarker for risk stratification and immunotherapy guidance, and highlights AP2S1 as a promising therapeutic target for translational intervention.
AVIL promotes osteosarcoma progression and cisplatin resistance via ARP2/3-mediated DNA damage repair.
Chen Z, Tang G, Lv X … +7 more , Ding G, Huang M, Chen Z, Dai S, Liu H, Zhang S, Cai L
Transl Oncol · 2026 Feb · PMID 41496412 · Full text
Osteosarcoma (OS) is the most common primary malignant tumor of bone that commonly occurs in adolescents with poor prognosis. Neoadjuvant chemotherapy with the MAP regimen (high-dose methotrexate (Methotrexate), doxorubi...
Osteosarcoma (OS) is the most common primary malignant tumor of bone that commonly occurs in adolescents with poor prognosis. Neoadjuvant chemotherapy with the MAP regimen (high-dose methotrexate (Methotrexate), doxorubicin, and cisplatin) is essential for the standardized OS therapeutic, the good response of which critically exceeds the patient survival. However, approximately 30-40 % of patients develop chemoresistance, leading to metastatic disease or recurrence. Understanding the molecular mechanisms underlying chemoresistance is crucial for improving clinical outcomes. In this study, AVIL was identified as a key gene correlated with OS progression and chemoresistance. AVIL overexpression was found to promote OS progression in vitro and in vivo by enhancing cell proliferation, migration, and invasion, while AVIL deficiency exerted the inverse phenotypes. In vivo experiments further confirmed that AVIL overexpression promotes tumor growth and suppresses apoptosis. Mechanistically, AVIL interacts with the ARP2/3 complex, a key regulator of DNA damage repair via actin polymerization and cytoskeletal dynamics. This interaction was confirmed to facilitate cisplatin resistance, with reduced DNA damage response and increased cell survival caused by AVIL overexpression. Furthermore, using patient-derived organoid (PDO) models, we demonstrated that CK666, an ARP2/3 inhibitor, enhanced the chemotherapy efficacy of cisplatin by increasing DNA damage response and reversing AVIL-mediated cisplatin resistance. These findings highlight AVIL as a potential therapeutic target and suggest that targeting the AVIL-ARP2/3 axis could serve as an alternative strategy to overcome chemoresistance during OS treatment.
Single-cell analysis identifies a stemness-associated tumor cell subpopulation and develops a prognostic scoring model in esophageal squamous cell carcinoma.
Ye W, Su W, Lei C … +2 more , Huang C, Du M
Transl Oncol · 2026 Feb · PMID 41496411 · Full text
Esophageal squamous cell carcinoma (ESCC) exhibits marked heterogeneity and poor prognosis, but the contribution of stemness‑related tumor cells remains unclear. Using single‑cell RNA sequencing, we identified eight tumo...
Esophageal squamous cell carcinoma (ESCC) exhibits marked heterogeneity and poor prognosis, but the contribution of stemness‑related tumor cells remains unclear. Using single‑cell RNA sequencing, we identified eight tumor subpopulations in ESCC, among which one cluster displayed prominent stem‑like and proliferative features with high expression of MKI67, STMN1, and UBE2C. Based on its marker genes, we established a stemness‑associated scoring model (SASM). Validation in independent TCGA and GSE53624 cohorts confirmed that higher SASM scores predicted shorter overall survival and reduced immune infiltration, particularly of CD8⁺ T cells. SASM scores were positively correlated with tumor mutational burden (TMB), and patients with high SASM and low TMB exhibited the poorest outcomes. Further analysis identified TFDP1 as a key gene associated with SASM and adverse prognosis, which was upregulated in tumor tissues and promoted ESCC cell proliferation in vitro. Overall, our study delineates stemness‑related tumor heterogeneity in ESCC, proposes a prognostic scoring system with immunological relevance, and highlights TFDP1 as a potential therapeutic target.
Induction chemotherapy with nedaplatin, docetaxel and 5-fluorouracil followed by concurrent nedaplatin and radiotherapy in locoregionally advanced nasopharyngeal carcinoma: A single arm, open label, phase II clinical trial.
Chen FZ, Deng Y, Yin WJ … +12 more , Wang MY, Yang F, Yang ZH, Zhou LP, Chen SD, Chen JL, Jiang XZ, Zhou AX, Ou YM, Liu JQ, Chen DP, Qi B
Transl Oncol · 2026 Feb · PMID 41496409 · Full text
PURPOSE: To evaluate the efficacy of nedaplatin in induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma. METHODS: In this prospective, single-arm, open-label phase...
PURPOSE: To evaluate the efficacy of nedaplatin in induction chemotherapy and concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma. METHODS: In this prospective, single-arm, open-label phase II trial, patients with newly diagnosed stage III-IVa (except T3-4N0) nasopharyngeal carcinoma were enrolled. Participants received three cycles of induction chemotherapy with docetaxel (60 mg/m² IV on days 1, 22, and 43), nedaplatin (60 mg/m² IV on days 1, 22, and 43), and fluorouracil (600 mg/m²/day as a continuous 120 h infusion on days 1-5, 22-26, and 43-47). This was followed by intensity-modulated radiotherapy with concurrent nedaplatin (100 mg/m² IV on days 1, 22, and/or 43) for two or three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. RESULTS: From March 2020 to November 2021, 32 patients were enrolled. With a median follow-up of 42.4 months (IQR, 35.4-45.2), 32 patients (100 %) achieved ORR at 12 weeks post-treatment. The 36-month PFS was 87.5 % (95 % CI, 76.1 %-98.8 %), and the 36-month OS was 100 %. The most common grade 3 or 4 adverse events during induction chemotherapy were neutropenia (9.4 %), diarrhea (9.4 %), leukopenia (6.2 %), fatigue (3.1 %) and hepatotoxicity (3.1 %). Mucositis (9.4 %) was the most common adverse events during concurrent chemoradiotherapy, followed by leukopenia (3.1 %), neutropenia (3.1 %), and thrombocytopenia (3.1 %). All adverse events were manageable. CONCLUSION: Induction chemotherapy with nedaplatin, docetaxel, and 5-fluorouracil, followed by concurrent nedaplatin with intensity-modulated radiotherapy, demonstrated promising antitumor activity and manageable toxicities in locoregionally advanced nasopharyngeal carcinoma patients. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov identifier: NCT04834206.
First functional evidence that a rare germline TP53β variant drives senescence-associated immune suppression and impairs apoptosis and cell migration in breast cancer patients.
Christowitz C, Olivier DW, van der Merwe N … +2 more , Kotze MJ, Engelbrecht AM
Transl Oncol · 2026 Feb · PMID 41496406 · Full text
INTRODUCTION: Pathology-supported genetic testing (PSGT), a personalized medicine framework established in South Africa, led to the identification of a rare germline tumour suppressor protein 53 (TP53) beta-isoform (β) v...
INTRODUCTION: Pathology-supported genetic testing (PSGT), a personalized medicine framework established in South Africa, led to the identification of a rare germline tumour suppressor protein 53 (TP53) beta-isoform (β) variant (NM_001126114.3, c.1018A>G, p.N340D) in a family with the Li-Fraumeni-like syndrome. While protein modeling predicted structural alterations consistent with impaired function, its pathogenicity remained unclear. AIM: To determine the functional impact of the TP53β N340D variant on cell proliferation, cell death, senescence, migration, and anti-tumour activity using a translational ex vivo model. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from female controls and breast cancer patients, with or without the TP53β N340D variant. Lipopolysaccharide (LPS)- and phytohemagglutinin-L (PHA-L)-stimulated proliferation was evaluated by a water-soluble tetrazolium 1 (WST-1) assay. Doxorubicin (DXR)-induced cell death was assessed using a WST-1 assay, flow cytometry, and western blotting. A senescence-associated beta-galactosidase assay and western blotting determined senescence. Migration and anti-tumour activity were assessed using a Transwell assay and co-culturing PBMCs with BT-549 spheroids. RESULTS: The TP53β N340D variant impaired DXR-induced cell death (p < 0.001), supported by reduced late apoptosis and decreased CASP3 and PARP activation. TP53β N340D PBMCs exhibited increased senescence (p < 0.01), potentially contributing to chemoresistance. Reduced LPS- and PHA-L-stimulated proliferation was dependent on cancer status. The variant reduced PBMC migration (p < 0.01), suggesting altered immune recruitment. Although anti-tumour activity appeared reduced in TP53β N340D PBMCs, spheroid size remained unchanged. CONCLUSIONS: This study provides supporting evidence for the pathogenicity of the TP53β N340D variant and highlights the importance of integrating functional genomics into PSGT to enhance medical decision-making.
Integrated spatial and single-cell transcriptomics reveals RPL8 as a prognostic biomarker and therapeutic target in hepatocellular carcinoma.
Tan J, Liang J, Li Y … +7 more , He J, Yin H, Wu H, Luo Y, Li M, Long F, Lin H
Transl Oncol · 2026 Feb · PMID 41496405 · Full text
BACKGROUND & AIMS: Ribosomal protein L8 (RPL8) is up-regulated in hepatocellular carcinoma (HCC), yet its clinical value and microenvironment role remain unclear. METHODS: Multi-omics (TCGA, CPTAC), scRNA-seq (GSE146115)...
BACKGROUND & AIMS: Ribosomal protein L8 (RPL8) is up-regulated in hepatocellular carcinoma (HCC), yet its clinical value and microenvironment role remain unclear. METHODS: Multi-omics (TCGA, CPTAC), scRNA-seq (GSE146115) and spatial transcriptomics were integrated; function was tested by RPL8 knockdown, proliferation/migration assays and drug-sensitivity screens. RESULTS: RPL8 mRNA/protein were markedly elevated (p < 0.001) with AUC 0.95 for diagnosis. High RPL8 independently predicted shorter overall (HR 1.42) and disease-specific survival (HR 1.35). Mechanistically, RPL8 co-activated MYC/G2M signaling, rewired glutathione metabolism and correlated with cell-cycle/DNA-repair scores (p < 0.001). scRNA-seq showed selective RPL8 enrichment in malignant hepatocytes and exhausted CD8T cells; spatial maps revealed tumor-confined expression inversely linked to immune infiltration (p < 0.01). Silencing RPL8 suppressed proliferation, migration and glutathione synthesis (p < 0.001), while sensitizing cells to sirolimus and sclareol (p < 0.05). CONCLUSIONS: RPL8 drives HCC progression and immune evasion, qualifying it as a diagnostic biomarker and therapeutic target.
BioMarrow: An accessible and reproducible 3D patient-derived bone marrow model for advancing research and clinical applications.
Lourenço D, Lopes R, Caetano J … +5 more , Barahona F, Rodrigues J, Queirós AC, Carneiro EA, João C
Transl Oncol · 2026 Feb · PMID 41421147 · Full text
Preclinical models for multiple myeloma (MM) often fail to recapitulate the complexity of the bone marrow (BM) microenvironment, limiting their utility for drug testing and translational research. There is an urgent need...
Preclinical models for multiple myeloma (MM) often fail to recapitulate the complexity of the bone marrow (BM) microenvironment, limiting their utility for drug testing and translational research. There is an urgent need for physiologically relevant, patient-adaptable platforms to support personalized therapeutic evaluation. We developed BioMarrow, a 3D ex vivo BM culture system using unmanipulated patient BM aspirates embedded in Matrigel. Culture conditions were optimized to sustain diverse hematopoietic, stromal and immune populations for up to 7 days. Spatial distribution, cytokine secretion and treatment responses were assessed via flow cytometry, immunohistochemistry, multiplex ELISA and cell viability assays. The model maintained key BM components characteristics of MM, supported stromal network formation and preserved cytokines such as IL-6 and TGF-β. Immune-effector cytokines were reduced, consistent with a tumour-permissive microenvironment. Drug testing with MM cell lines confirmed BioMarrow's ability to discriminate treatment sensitivity. BioMarrow captures essential features of the MM niche and offers a clinically relevant, short-term platform for ex vivo therapeutic screening. Its scalability and immune component preservation support future integration into personalized treatment workflows, including immunotherapy evaluation.
Evaluation of the anti-tumor efficacy of prodigiosin in papillary thyroid cancer cell and animal models.
Liu M, Huang J, Dai M … +10 more , Gao X, Ai Z, Hu W, Li Z, Wang F, Yang J, Liao H, Xie Y, Ying Y, Zeng X
Transl Oncol · 2026 Feb · PMID 41418402 · Full text
OBJECTIVE: To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC). METHODS: The anti-cancer effects of PG were systematically evaluated in vitro u...
OBJECTIVE: To investigate the anti-tumor efficacy and underlying molecular mechanisms of prodigiosin (PG) in papillary thyroid cancer (PTC). METHODS: The anti-cancer effects of PG were systematically evaluated in vitro using PTC cell lines and in vivo via xenograft mouse models. Cell viability and dose-response relationships were determined by CCK-8 assays. Anti-proliferative activity was assessed through colony formation and EdU incorporation assays. The impact on metastatic potential was examined by scratch wound healing and Matrigel-based transwell migration and invasion assays. Cell cycle distribution was analyzed using flow cytometry. RESULTS: In vitro, PG at 500 nM inhibited the growth of BCPAP and TPC-1 cells by 93.5 % and 89.2 %, respectively, as determined by colony formation assays. Migration and invasion of BCPAP cells were reduced by 90.7 % and 93.4 %, measured via scratch wound healing and transwell assays. PG treatment modulated epithelial-mesenchymal transition (EMT) markers both in vitro and in vivo, characterized by downregulating mesenchymal proteins and upregulating epithelial proteins, accompanied by changes in Wnt/β-catenin pathway-related proteins, indicating suppression of EMT. Flow cytometry revealed that PG induced G0/G1 cell cycle arrest in both BCPAP and TPC-1 cells. Furthermore, PG upregulated the sodium-iodide symporter (NIS), enhancing radioiodine uptake. Moreover, the treatment of PG significantly inhibited tumor growth without notable toxicity in vivo. CONCLUSION: PG exerts potent anti-tumor activity against PTC by simultaneously inhibiting proliferation, migration, and invasion, inducing cell cycle arrest, and enhancing radioiodine uptake, potentially through modulation of the Wnt/β-catenin signaling pathway. Our findings position PG as a highly promising, potentially transformative therapeutic candidate for PTC, offering a strategic approach to overcome conventional therapy resistance and improve clinical outcomes.
Multi-omics characterization identifies AHCY as a prognostic biomarker driving immunometabolic reprogramming in bladder cancer.
Peng Q, Zhang M, Zhao S … +6 more , Guo Y, Shan M, Su B, Mao S, Shi D, Lin Z
Transl Oncol · 2026 Feb · PMID 41411923 · Full text
INTRODUCTION: Bladder cancer (BLCA) is a heterogeneous malignancy with poor prognosis and limited biomarkers for risk stratification and therapy guidance. Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cyc...
INTRODUCTION: Bladder cancer (BLCA) is a heterogeneous malignancy with poor prognosis and limited biomarkers for risk stratification and therapy guidance. Adenosylhomocysteinase (AHCY), a key enzyme in the methionine cycle, has been implicated in tumor progression and epigenetic regulation, but its clinical and biological significance in BLCA remains unclear. METHODS: We performed an integrative pan-cancer and BLCA-focused analysis using TCGA, GTEx, and multiple independent datasets. Multi-omics data, including transcriptomic, genomic, epigenetic, immune, and drug sensitivity profiles, were systematically analyzed. Prognostic associations were evaluated by Cox and Kaplan-Meier analyses, and in vitro knockdown assays were conducted to assess AHCY function in BLCA cells. RESULTS: AHCY was significantly upregulated across diverse cancers and correlated with poor overall, disease-specific, and progression-free survival. In BLCA, AHCY overexpression was driven by copy number amplification and promoter hypomethylation, and was associated with enhanced cell cycle progression, DNA replication, and pyrimidine metabolism, while negatively linked to apoptosis and immune activation. High AHCY expression correlated with immune infiltration but impaired effector responses, predicted poor immunotherapy outcomes, and conferred resistance to chemotherapeutics and targeted agents across PRISM, CTRP, and GDSC datasets. Functional assays confirmed that AHCY depletion suppressed proliferation, induced apoptosis, and promoted ferroptosis by downregulating SLC7A11 and upregulating ACSL4 and 4-HNE. CONCLUSIONS: Our findings identify AHCY as a prognostic biomarker and immunometabolic regulator in BLCA, linking methionine metabolism to tumor progression, immune suppression, and drug resistance. AHCY holds promise as a therapeutic target and companion biomarker for precision oncology.
The stem cell atlas of lung adenocarcinoma: A stemness blueprint for prognosis and immunotherapy success.
Yin J, Jin X, Hu Z … +8 more , Yang H, Huo S, Sun F, Jiang W, Wang Q, Sui Q, Shi Y, Chen Z
Transl Oncol · 2026 Feb · PMID 41411922 · Full text
Cancer stem cells (CSCs) are involved in tumor initiation, metastasis, therapeutic resistance, and heterogeneity of aggressive lung adenocarcinomas (LUADs). Although identification of CSCs through cell surface markers ex...
Cancer stem cells (CSCs) are involved in tumor initiation, metastasis, therapeutic resistance, and heterogeneity of aggressive lung adenocarcinomas (LUADs). Although identification of CSCs through cell surface markers expression defines the CSC compartment, it provides little information on molecular mechanisms underlying the biological behaviors of CSCs. The CSC-driving tumor evolution path is also largely unknown due to technical difficulties. This study aimed to comprehensively depict the landscape of LUAD CSCs at the single-cell and molecular levels. Through flow cytometry and lineage tracing, we reconstructed LUAD CSCs trajectories with patient-derived samples and identified a persistent stem-like population with distinct molecular signatures through all tumor stages. CSC-related pathways, transcription factors (TFs) and metabolic characteristics were differentially expressed along LUAD progression, which revealed that developmental trajectory and tumor heterogeneity were driven by multistep transcriptional reprogramming of CSCs. Moreover, CSCs might promote LUAD progression through the S100A9-pNF-κB axis. We discovered a specific stemness signature with genetic profiles along the tumor progression and significantly correlated with clinical outcomes. Notably, by integrating bulk tumor data from TCGA, molecular clustering based on the CSC stemness signature well-distinguished clinical features and genomic or immune alterations, with the high stemness index group exhibiting reduced immune activity and a tendency towards cold tumors. Overall, our results provided unique perspectives into previously unappreciated molecular dynamics of CSC subpopulations driving LUAD evolution. The stemness signature tailored personalized risk assessment and immunotherapy strategies for individual LUAD patients.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe