Clinical & Translational Oncology[JOURNAL]
Sun
200 papers
L-type calcium channel-mediated lipid metabolic reprogramming in gastric adenocarcinoma progression.
Cui M, Cheng S, Wen X … +5 more , Yang H, Huang Y, Pan L, Wei S, Huang H
Transl Oncol · 2026 May · PMID 41861661 · Full text
BACKGROUND: l-type calcium channels (LTCCs) play an important role in tumorigenesis, but their expression profile, functional significance, and therapeutic potential in gastric adenocarcinoma (GAC) remain unclear. Concur...
BACKGROUND: l-type calcium channels (LTCCs) play an important role in tumorigenesis, but their expression profile, functional significance, and therapeutic potential in gastric adenocarcinoma (GAC) remain unclear. Concurrently, aberrant lipid metabolism is widely acknowledged as a key driver of GAC progression, but its upstream regulatory mechanisms have yet to be fully elucidated. This study was designed to explore the association between LTCCs and lipid metabolic reprogramming in GAC and to investigate its influence on GAC progression and clinical outcomes. METHODS: The expression profiles of LTCCs family members in GAC were analyzed using the TCGA database. Gastric cancer cells were treated with the LTCCs antagonist (+)-Bay-K-8644, and its effect on the malignant phenotype of the cells was detected by CCK-8, clone formation, scratch healing and transwell assay. Metabolic changes were analyzed by UPLC-Q-TOF-MS metabolomics. The role of lipid metabolism in the regulation of LTCCs was verified by palmitic acid (PA) backfill assay. RESULTS: Bioinformatics analysis showed that Voltage-dependent LTCCs subunit alpha-1D (CACNA1D) was up-regulated in GAC. CACNA1D had excellent diagnostic value and its high expression was associated with poor prognosis. (+)-Bay-K-8644 significantly inhibited gastric cancer cells' proliferation, clone formation, and migration ability. Metabolomics analysis revealed that (+)-Bay-K-8644 treatment resulted in reprogramming of lipid metabolism. Exogenous PA was able to partially reverse the anticancer effects of (+)-Bay-K-8644 and restore cell proliferation and migration. CONCLUSIONS: This study elucidated the unique expression pattern of LTCCs in GAC for the first time, and confirmed that LTCCs antagonism exerts anticancer effects by inducing reprogramming of lipid metabolism. These findings provide a theoretical basis for repositioning calcium channel blockers for GAC therapy and suggest that combined targeting of calcium channels and lipid metabolism may become a new strategy for GAC treatment.
Exploring survival-associated transcriptomic subtypes in ovarian cancer using RNAseq from FFPE tissues in a clinical trial cohort.
Kjeldsen MK, Bagger FO, Roed H … +18 more , Nyvang GB, Haslund CA, Knudsen AO, Motavaf AK, Malander S, Anttila M, Lindahl G, Mäenpää J, Dimoula M, Werner T, Iversen TZ, Hietanen S, Fokdal L, Dahlstrand H, Bjørge L, Birrer M, Mirza MR, Rossing M
Transl Oncol · 2026 May · PMID 41861658 · Full text
OBJECTIVE: Transcriptomic subtyping is not yet standardized for prognostic use in epithelial ovarian cancer (EOC). This study aims to validate RNA sequencing (RNAseq) from formalin-fixed, paraffin-embedded (FFPE) tissues...
OBJECTIVE: Transcriptomic subtyping is not yet standardized for prognostic use in epithelial ovarian cancer (EOC). This study aims to validate RNA sequencing (RNAseq) from formalin-fixed, paraffin-embedded (FFPE) tissues and to evaluate survival-associated transcriptomic subtypes and differentially expressed genes (DEGs) in a clinical trial cohort. METHODS: An exploratory post hoc analysis was conducted on FFPE samples from patients enrolled in the ENGOT-ov24/NSGO-AVANOVA1&2 trial. RNA was extracted and sequenced, and gene expression analysis was performed to classify subtypes using established, microarray-based, algorithms. Differentially expressed genes (DEGs) were identified based on survival groups, and survival outcomes were analyzed using Kaplan-Meier curves. RESULTS: Of 96 eligible samples, 82 were included in the final analysis. Subtype classifications showed moderate agreement across RNAseq data formats. However, gene expression variability showed inconsistent concordance with clinical metadata and molecular subtypes. Eighteen genes were differentially expressed between long- and short-term survivors. Notably, DPEP3 and SLC14A1, were significantly upregulated in long-term survivors. Despite distinct expression patterns, no significant survival differences were observed between subtypes. CONCLUSIONS: This study demonstrates the feasibility of using RNAseq on FFPE tissue in EOC, while also highlighting challenges of applying microarray-based transcriptomic subtypes to RNAseq data. Transcriptomic analysis identified potential prognostic gene candidates but also highlighted the need to refine classification tools. Further research is essential to improve the molecular classification of EOC, thereby enhancing prognostic accuracy and guiding future therapeutic strategies.
Single-cell inflammatory signaling defines a novel CEP135 endothelial subtype associated with glioma progression.
Ji Z, Kahlert UD, Wu S … +7 more , Dumitru CA, Sandalcioglu E, Zhang J, Wang D, Qu J, Shi W, Yan B
Transl Oncol · 2026 May · PMID 41861657 · Full text
BACKGROUND: Chronic inflammation is a key driver of glioma progression, but its cellular organization within the tumor microenvironment remains poorly understood. METHODS: This study employed an integrated multi-omics an...
BACKGROUND: Chronic inflammation is a key driver of glioma progression, but its cellular organization within the tumor microenvironment remains poorly understood. METHODS: This study employed an integrated multi-omics analysis strategy, combining bulk transcriptomics, proteomics, and glioma cell line expression data with single-cell RNA sequencing data from paired gliomas and adjacent normal brain tissues. Inflammatory signaling activity was quantitatively assessed using pathway-level scoring methods, endothelial cell heterogeneity was analyzed at single-cell resolution, and pseudo-temporal trajectory analysis and cell-cell communication analysis were further conducted. Immunohistochemical analysis was performed using human glioma brain tissue samples from our center to independently validate key findings at the protein level. RESULTS: Bulk transcriptomics analysis revealed significantly activated inflammatory signals in glioblastomas. Single-cell analysis identified a highly inflammatory endothelial cell subtype that was significantly enriched in tumor tissues. Cell communication analysis further revealed enhanced signal output capabilities and participation in neurally-related ligand-receptor interactions. CEP135 was specifically enriched in this endothelial cell subtype and showed consistent upregulation of both transcriptional and protein levels across multiple independent datasets. Immunohistochemical analysis of glioma brain tissue from our center confirmed that CEP135 is primarily localized in tumor-associated endothelial regions, and its expression level was significantly correlated with increasing tumor grade.High CEP135 expression was associated with poor treatment response, shorter survival outcomes. CONCLUSION: This study identified a innovative CEP135+inflammation-associated endothelial cell subtype and established CEP135 as a key biomarker linking endothelial inflammation reprogramming, tumor progression, and adverse clinical outcomes.
Genomic landscape of pleural mesothelioma in Japanese patients: A comprehensive analysis using nationwide database.
Taniguchi H, Akagi K, Fukuda T … +17 more , Honda T, Kurohama H, Ueki N, Matsuoka Y, Udo E, Yahata S, Miura S, Tomono H, Honda N, Dotsu Y, Matsuo M, Takemoto S, Sato I, Okano S, Nakashima M, Mukae H, Ashizawa K
Transl Oncol · 2026 May · PMID 41855858 · Full text
Pleural mesothelioma (PM) is a rare and aggressive malignancy. The development of novel therapeutic strategies targeting PM remains an unmet clinical need. However, comprehensive genomic data from Asian populations, part...
Pleural mesothelioma (PM) is a rare and aggressive malignancy. The development of novel therapeutic strategies targeting PM remains an unmet clinical need. However, comprehensive genomic data from Asian populations, particularly from Japanese patients, are limited. This study aimed to elucidate the genomic landscape of PM in Japanese patients using the nationwide Center for Cancer Genomics and Advanced Therapeutics (C-CAT) genomic database. A total of 211 patients registered between June 2019 and March 2025 were analyzed. The most frequent genetic alterations were in BAP1, NF2, TP53, CDKN2A/B, and MTAP. The median tumor mutation burden (TMB) was 1.26, and no microsatellite instability-high patients were detected. The median overall survival (OS) after first-line treatment was 30.6 months. Patients treated with immune checkpoint inhibitors (ICIs) had a significantly better OS than those who did not receive ICIs. In univariate and multivariate analyses, TP53 alterations and high TMB (cutoff value of 1.6) were associated with poor prognosis. These results suggest that integrating clinical and genomic data can enhance prognostic stratification and contribute to the development of precision medicine for PM. This study provides the first large-scale genomic characterization of Japanese PM patients with C-CAT and highlights potential biomarkers for future therapeutic development.
Ex vivo organotypic culture of liposarcoma effectively models in vivo supratherapeutic paclitaxel localized drug delivery.
Caturegli I, Liu R, Rivera V … +4 more , Taub O, Grinstaff MW, Colson YL, Raut CP
Transl Oncol · 2026 May · PMID 41855856 · Full text
BACKGROUND: Retroperitoneal sarcomas (RPS) exhibit a high locoregional recurrence rate after macroscopically complete surgical resection. Systemic therapies have limited efficacy and significant adverse effects. Sarcoma...
BACKGROUND: Retroperitoneal sarcomas (RPS) exhibit a high locoregional recurrence rate after macroscopically complete surgical resection. Systemic therapies have limited efficacy and significant adverse effects. Sarcoma cell lines are susceptible to paclitaxel (PTX), a microtubule stabilizer, in 2-dimensional (2-D) monolayer cell culture, but resistant in animal models. When locally delivered via drug-eluting buttresses supratherapeutic concentrations are achieved and PTX becomes efficacious. Due to the limitations of 2-D culture, we establish an organotypic culture system to model the mechanisms by which supratherapeutic and prolonged exposure of PTX is effective. METHODS: Liposarcoma tumors (LP6) were established subcutaneously in NU/J mice. Tumors were harvested, sliced with a vibratome (250 µm thick), and cultured on permeable trans wells. RESULTS: Organotypic culture viability was maintained up to 7 days with greater than 50 % viability. Tumor slices were composed of 82 % ± 7 % human liposarcoma cells with the remainder being mouse stroma as determined by CD44 staining. Under 4-day exposure, IC of PTX with organotypic culture shifted 7000 rightward as compared to 2-D culture. A subset of 17 genes was significantly differentially expressed as compared to untreated controls, while no genes were differentially expressed after 1 day of treatment. Gene set enrichment analysis demonstrated enrichment in apoptotic, extracellular matrix, cell motility, and cell cycle pathways. Caspase-8 activation occurred only at 10,000 ng/mL and 4-days of PTX or greater. CONCLUSION: This study reports a reproducible, clinically relevant organotypic culture liposarcoma model, which can serve as an intermediary between in vitro and in vivo studies.
Personalized and HPV cancer vaccines in head and neck squamous cell carcinoma: from concept to clinical implementation.
Filippini DM, Le Tourneau C
Transl Oncol · 2026 May · PMID 41830840 · Full text
Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy, with limited survival improvements despite recent advances with immune checkpoint inhibitors (ICIs). Within this context, personalized neoan...
Head and neck squamous cell carcinoma (HNSCC) remains a challenging malignancy, with limited survival improvements despite recent advances with immune checkpoint inhibitors (ICIs). Within this context, personalized neoantigen vaccines and HPV-targeted therapeutic vaccines are emerging as innovative strategies aimed at enhancing antitumor immunity. Personalized vaccines exploit tumor-specific mutational landscape to generate highly individualized T cell responses, demonstrating favorable safety profiles and durable immunogenicity in early-phase trials. Compounds such as TG4050, mRNA-4157, and PGV001 have shown early, hypothesis-generating signals of activity (from small early-phase studies), particularly in the adjuvant setting. HPV-targeted vaccines, including PDS0101, BNT113, and CUE-101, are being explored in HPV-positive HNSCC, mainly in combination with ICIs. While some early clinical activity has been observed, these signals should be interpreted cautiously given limited sample sizes, heterogeneous populations, and exploratory endpoints in many studies, and randomized trials such as ISA101b have failed to show survival benefits over ICIs alone. Overall, therapeutic vaccination appears safe and immunologically active, yet its efficacy is constrained by the immunosuppressive tumor microenvironment. The greatest clinical potential of therapeutic vaccination may lie in earlier disease stages, where the tumor burden is lower and immune modulation more feasible. Further clinical and translational research is needed to define the optimal integration of vaccine-based therapies into multimodal treatment paradigms for HNSCC.
Molecular mechanisms and therapeutic targeting implications of ER/mTOR signaling axis-driven tumor progression in aggressive meningiomas.
Yao H, Zhu K, Li S … +7 more , Hei J, Wang S, Li W, Ye T, Jiang W, Martin T, Zhang S
Transl Oncol · 2026 Apr · PMID 41794007 · Full text
PURPOSE: Aggressive meningiomas pose substantial clinical challenges because of their high rates of recurrence. The aim of this study is to investigate the mechanistic role of estrogen receptor (ER)-mediated mTOR hyperac...
PURPOSE: Aggressive meningiomas pose substantial clinical challenges because of their high rates of recurrence. The aim of this study is to investigate the mechanistic role of estrogen receptor (ER)-mediated mTOR hyperactivation in promoting meningioma progression and to evaluate the therapeutic potential of targeting this signaling axis with tamoxifen. METHODS: Analyses involving data from clinical registries have established sex as a predictor of adverse outcomes, while multiomics investigations have revealed the overexpression of ER in advanced-grade and recurrent tumors. Functional validation was conducted using ER knockdown models. Mechanistic insights were obtained through RNA sequencing, with orthogonal validation performed via qPCR and Western blotting, with a focus on regulators of the mTOR pathway (RICTOR, PIK3CA, and DEPTOR). Therapeutic efficacy was evaluated in meningioma cell models through pharmacological inhibition using tamoxifen. RESULTS: Clinical analysis was used to identify sex as a predictor of adverse outcomes, revealing that ER overexpression is significantly correlated with advanced tumor grades. Silencing of the ER markedly reduced malignant phenotypes, leading to decreased cell proliferation and invasion, while also inducing apoptosis. Mechanistically, ER activation resulted in the upregulation of RICTOR and PIK3CA expression, alongside suppression of DEPTOR, which directly activated mTOR signaling. Tamoxifen exhibited potent antitumor effects by reversing this oncogenic signaling cascade. CONCLUSION: This study revealed that the ER/mTOR axis is associated with sex-linked therapeutic vulnerability in aggressive meningiomas. This finding provides mechanistic evidence for ER-driven mTOR activation via the dysregulation of RICTOR/PIK3CA-DEPTOR. The demonstrated efficacy of tamoxifen supports its clinical repurposing as a targeted therapy for ER-positive meningiomas, offering a biologically rational strategy to address therapeutic resistance in this challenging malignancy.
Development and characterization of anti-CXCR4 chimeric antigen receptor T cells.
Seir G, Bubb QR, Sotillo E … +3 more , Gruber T, Richards RM, Czechowicz A
Transl Oncol · 2026 Apr · PMID 41780186 · Full text
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) are aggressive hematologic malignancies characterized by dysregulation of normal hematopoiesis and acquisition of stem-like, self-renewing properties le...
Acute Myeloid Leukemia (AML) and Acute Lymphoblastic Leukemia (ALL) are aggressive hematologic malignancies characterized by dysregulation of normal hematopoiesis and acquisition of stem-like, self-renewing properties leading to oncogenesis. Current treatments primarily rely on toxic chemotherapies with or without hematopoietic stem cell transplantation (HSCT). These are associated with significant short- and long-term side effects and sub-optimal outcomes across treatment of both AML and ALL. Improved HSCT methods are needed that can both eliminate leukemic cells and improve outcomes. The C-X-C chemokine receptor type 4 (CXCR4) plays a key role in both normal hematopoiesis and leukemogenesis by attracting and retaining cells in the bone marrow niche. It has been targeted using antibody or drug-based approaches leading to clinical trials and therapeutics across indications. In the context of chimeric antigen receptor (CAR) T cells, it has been expressed as a co-receptor to improve bone marrow homing and amplify tumor eradication. Here, we confirm high CXCR4 expression across AML and ALL using publicly available tumor transcriptomic datasets. Subsequently, we report the development of anti-CXCR4 CAR-T cells that demonstrate potent activity against a panel of leukemic cell lines in vitro without activity against other T cells. We observe decreased CXCR4 protein expression in CAR-positive populations indicating a potential pathway for T cell survival. Our findings support the potential of anti-CXCR4 CAR-T cells as a broadly applicable strategy for eliminating both AML and ALL, with possible extension to hematopoietic stem and progenitor cells, unlocking the potential of this strategy as a dual HSCT-conditioning and anti-leukemia agent.
Single-cell analysis of TIGD genes in hepatocellular carcinoma: Prognostic value and functional characterization.
Liu J, Chen X, Liu C … +2 more , Yang C, Li B
Transl Oncol · 2026 Apr · PMID 41775084 · Full text
BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapies. Although transposable element-derived genes are increasingly linked to tumorigenesis, the role of the TIGD family in HCC remains...
BACKGROUND: Hepatocellular carcinoma (HCC) is an aggressive cancer with limited therapies. Although transposable element-derived genes are increasingly linked to tumorigenesis, the role of the TIGD family in HCC remains unclear. This study examined the expression, clinical significance, and stemness-related features of TIGDs in HCC, emphasizing their prognostic and therapeutic potential. METHOD: TIGD expression was analyzed using TCGA data via GEPIA2, cBioPortal, and Kaplan-Meier Plotter, with protein validation from the Human Protein Atlas. Single-cell RNA-seq data (GSE242889) were used to examine TIGD expression across hepatic cell types. Survival and Cox regression analyses assessed prognostic value, while functional enrichment and immune infiltration analyses explored biological roles. TIGD5-high and TIGD5-low epithelial subsets were compared for functional features and cell-cell communication. RESULTS: TIGD1, 3, 4, 5, 6, and 7 were significantly upregulated in HCC. High TIGD4, TIGD5, and TIGD6 expression correlated with poorer overall survival and served as independent prognostic markers. TIGD5 exhibited the broadest and highest expression across immune and stromal compartments. Stratification of epithelial cells into TIGD5-high and TIGD5-low subsets revealed distinct functional phenotypes: TIGD5-high cells showed enrichment in extracellular matrix organization, growth factor signaling, and immune regulatory pathways, with enhanced communication probability within the tumor microenvironment. Notably, TIGD5+ epithelial cells demonstrated increased interaction strength and MIF signaling pathway engagement compared to TIGD5- counterparts. Functional analyses indicated roles in RNA splicing, DNA replication, and cell-cycle regulation. TIGDs also showed associations with immune infiltration, particularly Th2 cells. CONCLUSION: TIGD4, TIGD5, and TIGD6 exhibit oncogenic potential and may serve as prognostic biomarkers and therapeutic targets in HCC. Their stem-cell-associated expression highlights a novel connection between transposable element-derived genes and liver cancer stemness.
The Hippo pathway in clear cell renal cell carcinoma (ccRCC): a nexus with the VHL disruption?
Waeckel T, Lefranc R, Waeckel M … +4 more , Riffet M, Tillou X, Levallet G, Bazille C
Transl Oncol · 2026 Apr · PMID 41764979 · Full text
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) represents 70% of kidney cancers, with 20-50% recurrence risk after surgery. Despite therapeutic advances, no reliable biomarkers have been identified for patient strat...
BACKGROUND: Clear cell renal cell carcinoma (ccRCC) represents 70% of kidney cancers, with 20-50% recurrence risk after surgery. Despite therapeutic advances, no reliable biomarkers have been identified for patient stratification or treatment response prediction. While VHL gene alterations are well-established in ccRCC pathogenesis, the role of the Hippo pathway remains underexplored despite ample evidence of its involvement. OBJECTIVE: This review synthesizes current knowledge on Hippo pathway alterations in ccRCC and examines its crosstalk with the VHL/HIF axis, identifying potential biomarkers and therapeutic targets. STRATEGY: We comprehensively analyzed literature on Hippo pathway components in ccRCC, focusing on molecular mechanisms, clinical correlations, and interactions with VHL signaling. RESULTS: Multiple Hippo pathway alterations characterize ccRCC: RASSF1A hypermethylation, NF2 mutations (particularly in aggressive variants), SAV1 downregulation associated with 14q loss, and LATS1/2 methylation-mediated inactivation. These changes result in YAP/TAZ nuclear accumulation and oncogenic transcription. Importantly, chromosome 3p loss simultaneously disrupts both VHL and RASSF1, creating a unique double-hit scenario. The VHL-Hippo crosstalk operates through multiple mechanisms: HIF-induced GPRC5A and VEGFR signaling inhibit LATS1/2 phosphorylation, promoting YAP/TAZ activation, while active YAP/TAZ enhances pro-angiogenic gene transcription, amplifying hypoxic responses. Low expression of RASSF1A, SAV1, and LATS1/2, coupled with high YAP/TAZ activity, correlates with advanced tumor stage, higher grade, and poorer survival. CONCLUSIONS: The Hippo pathway represents a critical yet underappreciated dimension of ccRCC biology, offering promising biomarkers for risk stratification and novel therapeutic targets. The Hippo-VHL nexus presents multiple intervention points that could enhance current treatment.
A2AR as a key target for immune microenvironment remodeling in prostate cancer.
Yan L, Yang Z, Zhao X … +2 more , Chen Y, Wang Z
Transl Oncol · 2026 Apr · PMID 41763068 · Full text
This study elucidates the critical role of adenosine A2A receptor (A2AR) signaling in prostate cancer progression through comprehensive molecular characterization and clinical validation, demonstrating that A2AR overexpr...
This study elucidates the critical role of adenosine A2A receptor (A2AR) signaling in prostate cancer progression through comprehensive molecular characterization and clinical validation, demonstrating that A2AR overexpression in prostate cancer cells drives profound immunosuppression via coordinated upregulation of CD73-mediated adenosine production, subsequent activation of immunosuppressive pathways including ARG1, TGF-β, and IL-10 secretion, and induction of immune checkpoint molecules PD-L1 and Galectin-9, which collectively promote myeloid-derived suppressor cell expansion and CD8 T cell exhaustion while creating an immunologically privileged tumor microenvironment. Clinical correlation analyses across multiple patient cohorts reveal that elevated A2AR expression serves as a powerful independent predictor of aggressive disease progression and poor clinical outcomes, particularly in metastatic castration-resistant prostate cancer, where it exhibits stronger prognostic value than in other solid tumors. A2AR activation not only helps tumors resist immune checkpoint inhibitors but also blocking A2AR can work well with PD-1/PD-L1 treatments by reversing the immune suppression caused by adenosine and boosting the body's ability to fight tumors. The potential for using these findings in real-world clinical settings is backed by models showing that combining A2AR expression with adenosine pathway activity and immune profiling greatly improves the accuracy of risk assessment compared to standard prognostic markers, while earlier studies show that targeting this pathway could be a viable treatment option. These results collectively position A2AR as a master regulator of prostate cancer immunosuppression and a promising biomarker-guided therapeutic target, particularly for combination immunotherapy approaches in advanced disease settings where current treatment options remain limited.
Markers of immune activation and immunotherapy responsiveness are increased in 3D Pancreatic cancer organoids when primed with photodynamic- and chemo-therapy.
Cabral FV, Quilez-Alburquerque J, Szoo MJ … +3 more , de Silva P, Saad MA, Hasan T
Transl Oncol · 2026 Apr · PMID 41762540 · Full text
Pancreatic ductal adenocarcinoma (PDAC) remains highly resistant to chemotherapy and immunotherapy due to a dense tumor stroma and an immunosuppressive tumor microenvironment. In this study, we explored whether the photo...
Pancreatic ductal adenocarcinoma (PDAC) remains highly resistant to chemotherapy and immunotherapy due to a dense tumor stroma and an immunosuppressive tumor microenvironment. In this study, we explored whether the photodynamic priming (PDP) effect, a fallout of Photodynamic therapy (PDT), an approved treatment, could improve the treatment responses in 3D mouse-derived organoids. The organoids reproduced key features of pancreatic tumors and showed strong resistance to chemotherapy (nanoliposomal irinotecan, nal-IRI) and immune checkpoint inhibitor (anti-PD-1) when used alone. PDP overcame this resistance by enhancing the uptake and activation of nal-IRI, thereby increasing tumor cell death. PDP also triggered immunogenic cell death, marked by the release of danger signals that promote immune activation. When organoids were co-cultured with autologous peripheral blood mononuclear cells (PBMCs), PDP enhanced immune-mediated tumor killing. Notably, combining PDP with low doses of chemotherapy and PD-1 blockade resulted in complete tumor eradication. These effects were associated with increased immune activation and improved responsiveness to immunotherapy. Together, these findings show that PDP remodels the pancreatic tumor microenvironment, enhances chemotherapy efficacy, and sensitizes tumors to immune checkpoint inhibitors. This strategy uses clinically approved agents and offers a promising, translatable approach to overcoming treatment resistance in pancreatic cancer.
Construction and validation of golgi apparatus-related genes as predictors of the immune microenvironment and prognosis in colorectal cancer.
Chen J, Wang F
Transl Oncol · 2026 Apr · PMID 41762539 · Full text
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer globally, and the identification of novel biomarkers remains an urgent priority in clinical practice and research. Although the Golgi apparatus plays a...
BACKGROUND: Colorectal cancer (CRC) is the third most common cancer globally, and the identification of novel biomarkers remains an urgent priority in clinical practice and research. Although the Golgi apparatus plays a crucial role in tumorigenesis and cancer progression, its role in CRC remains unclear. METHODS: A comprehensive bioinformatics analysis of the transcriptome was conducted using the TCGA and GSE87211 datasets. A reliable risk signature model based on Golgi apparatus - related genes (GARGs) was constructed. Subsequently, we performed an in - depth single - cell RNA sequencing analysis. Finally, based on the consistent evidence across all analytical layers, GDI1 was selected for subsequent functional validation in cellular assays. RESULTS: By integrating univariate Cox regression and LASSO analysis, we identified a five-GARG signature to construct a prognostic model. This model stratified patients into high- and low-risk groups with significantly different overall survival. The high-risk group was associated with elevated stromal and ESTIMATE scores, along with increased infiltration of monocytes and M0 macrophages, suggesting a potentially more immunosuppressive and tumor-promoting microenvironment. Bioinformatic predictions indicated that the high-risk group might show enhanced sensitivity to Dasatinib, Sapitinib, and SB216763; this was preliminarily supported by our subsequent in vitro drug sensitivity assays. Cell-cell communication analysis suggested that macrophages might primarily influence the microenvironment through the tumor necrosis factor (TNF) signaling pathway. Critically, functional experiments demonstrated that silencing GDI1 significantly inhibited cell proliferation and migration and induced apoptosis, supporting its potential oncogenic role in COAD. CONCLUSION: Collectively, our work links GARG expression to CRC prognosis and immune features, and functionally implicates GDI1 in tumor cell aggressiveness, supporting its further study as a potential therapeutic target.
From prostate specific antigen to genomic signatures: Advances in biomarkers for prostate cancer diagnosis and prognosis.
Hamed NW, Elbeljihy HS, Hussin SA … +3 more , Fouda RM, Oy EK, W Magar R
Transl Oncol · 2026 Apr · PMID 41762538 · Full text
Prostate cancer is one of the most prevalent malignancies affecting men worldwide. It arises from the uncontrolled proliferation of abnormal cells within the prostate gland, an essential component of the male reproductiv...
Prostate cancer is one of the most prevalent malignancies affecting men worldwide. It arises from the uncontrolled proliferation of abnormal cells within the prostate gland, an essential component of the male reproductive system, and exhibits highly variable clinical behaviour, ranging from indolent, localised tumours to aggressive, metastatic disease. Early detection significantly improves treatment outcomes and survival rates, emphasising the urgent need for more sensitive and specific diagnostic approaches. This review provides a comprehensive overview of diagnostic and prognostic biomarkers associated with prostate cancer, highlighting their potential in early detection and disease monitoring. Traditional biomarkers such as digital rectal examination (DRE), prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and alkaline phosphatase (ALP) are discussed alongside emerging molecular markers that offer enhanced accuracy and predictive value. These include PCA3, SelectMDx, ExoDx Prostate (EPI), bone-specific ALP (BALP), 4Kscore, circulating tumour cells (CTCs), prostate health index (PHI), Oncotype DX Genomic Prostate Score (GPS), Decipher test, and ERG gene fusion. Additionally, the review addresses key genetic alterations implicated in prostate carcinogenesis, including mutations in BRCA1/2, HOXB13, and PTEN deletions, as well as changes in the androgen receptor pathway. By evaluating recent advancements and applications of these biomarkers, this review aims to enhance understanding of their role in improving early diagnosis, prognosis, and personalised management of prostate cancer.
Molecular epidemiology of the expression of urokinase plasminogen activator receptor-associated protein (uPARAP) in mesenchymal malignancies.
Wang CC, Barkholt P, Wozniak A … +9 more , Vanleeuw U, Lee CJ, De Sutter L, De Cock L, Verbeeck K, Engelholm LH, Lynch C, Mumberg D, Schöffski P
Transl Oncol · 2026 Apr · PMID 41734474 · Full text
INTRODUCTION: Sarcomas are highly heterogenous and rare malignant tumors derived from mesenchymal cells. The current standard treatments for advanced disease have low response rates and are typically associated with cons...
INTRODUCTION: Sarcomas are highly heterogenous and rare malignant tumors derived from mesenchymal cells. The current standard treatments for advanced disease have low response rates and are typically associated with considerable toxicity. The aim of this study was to investigate the expression of a potential novel therapeutic target and its clinical correlation in sarcomas, namely urokinase plasminogen activator receptor-associated protein (uPARAP/Endo180/CD280). MATERIALS AND METHODS: We evaluated uPARAP expression in various sarcoma subtypes and in normal tissues using 12 tissue microarrays. Expression was assessed on immunohistochemically stained slides and scored according to staining intensity and the percentage of positive tumor cells. Clinical correlations between uPARAP expression and selected parameters (gender and sample origin) were analyzed using generalized estimating equations, and survival outcomes were evaluated with Kaplan-Meier and log-rank tests. RESULTS: Our results demonstrated limited uPARAP expression in normal tissues, while high expression was observed in the majority of analyzed sarcoma subtypes, particularly high (>80% of highly positive cases) in fibrosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, malignant peripheral nerve sheath tumor, and various bone sarcomas. Based on the correlation analyses between uPARAP expression and selected clinical parameters or survival outcomes, most subtypes did not show a statistically significant association. CONCLUSION: In conclusion, this study highlights the potential of uPARAP as an innovative target for targeted treatments, such as novel antibody-drug conjugates in sarcoma.
Lactylation profiling reveals novel biomarkers and immune interactions in pancreatic cancer.
Xu D, Chen Q, Wang L … +4 more , Li L, Cheng K, Liu X, Lin K
Transl Oncol · 2026 Apr · PMID 41734473 · Full text
Pancreatic cancer, known for its aggressive nature and poor prognosis, often eludes early detection and effective treatment. This study investigates the underexplored terrain of protein lactylation in pancreatic cancer t...
Pancreatic cancer, known for its aggressive nature and poor prognosis, often eludes early detection and effective treatment. This study investigates the underexplored terrain of protein lactylation in pancreatic cancer to identify potential biomarkers and understand its immunological implications. Proteomic and transcriptomic analyses were conducted to profile lactylation changes, identifying 11 upregulated and 1 downregulated lactylation-related proteins. Intersection analysis between proteomics and transcriptomics highlighted four key genes (COQ9, GAA, LYST and TP53) with consistent expression trends, suggesting their central role in the lactylation pathway within pancreatic cancer. ROC curve analysis underscored the diagnostic potential of GAA and LYST, with AUCs over 0.9. Further, ssGSEA revealed significant correlations between these core genes and various immune cells, indicating an immune-modulatory role. Notably, most core lactylation-related genes were positively associated with immune checkpoint molecules, barring COQ9. GSEA of gene expression groups delineated three conserved upregulated KEGG pathways, with additional REACTOME pathway analysis uncovering 68 conserved pathways. These findings highlight lactylation's involvement in pancreatic cancer progression and its possible exploitation for diagnostic and therapeutic advancements.
SELE is associated with reduced breast cancer susceptibility: Evidence from Mendelian randomization and single-cell transcriptome.
Chen H, Hu W, Liu R … +2 more , Liu Q, Cheng X
Transl Oncol · 2026 Apr · PMID 41722201 · Full text
BACKGROUND: The role of circulating proteins in breast cancer (BC) early diagnosis remains unclear. We investigated genetically predicted associations between circulating proteins and BC risk using Mendelian randomizatio...
BACKGROUND: The role of circulating proteins in breast cancer (BC) early diagnosis remains unclear. We investigated genetically predicted associations between circulating proteins and BC risk using Mendelian randomization (MR). This study aims to identify novel protein biomarkers through an integrative multi-omics approach. METHODS: Using a two-sample MR framework, we assessed genetically determined circulating protein associations with BC risk/subtypes. Analysis incorporated large-scale protein quantitative trait loci (pQTL) and genome-wide association studies (GWAS) data, strengthened by cross-validation, sensitivity analyses (MR-Egger, MR-PRESSO), and meta-analysis. We further performed genetic colocalization, molecular docking, and phenome-wide MR (PheWAS-MR). Bulk and single-cell RNA sequencing data were analyzed to compare gene expression of causal proteins between healthy and BC tissues. This multi-layered validation enhances the robustness of causal inference. RESULTS: Three circulating proteins are associated with reduced BC risk-SELE (OR = 0.98, 95 % CI: 0.97-0.98), CDH1 (OR = 0.94, 95 % CI: 0.93-0.95), ALPI (OR = 0.95, 95 % CI: 0.94-0.96). CNTNAP2 is associated with elevated BC risk (OR = 1.02, 95 % CI: 1.01-1.03). Colocalization supported shared causal variants for SELE and ALPI. Molecular docking simulation indicates high binding affinity of SELE-simvastatin. SELE expression was significantly reduced in endothelial cells of BC tissue, and PheWAS-MR revealed SELE's association with 123 phenotypes, highlighting its extensive pleiotropic effects. CONCLUSIONS: This study provides robust genetic evidence for the causal roles of SELE, CDH1, and ALPI in reducing BC risk. The integrative proteomic-genetic-transcriptomic approach identifies potential therapeutic targets and offers new insights into BC pathogenesis, presenting hypotheses for clinical validation.
REST-driven upregulation of SFXN3 promotes AML progression via Wnt/β-catenin activation and confers decitabine resistance.
Wang X, Huang Y, Sun M … +7 more , Cai S, Hu X, Zheng Y, Fang S, Li S, Tu Y, Tang H
Transl Oncol · 2026 Apr · PMID 41720050 · Full text
One of the most diverse types of blood cancer is acute myeloid leukemia, or AML, and there remains an urgent need to identify novel molecular targets for its diagnosis and treatment. The present investigation identified...
One of the most diverse types of blood cancer is acute myeloid leukemia, or AML, and there remains an urgent need to identify novel molecular targets for its diagnosis and treatment. The present investigation identified Sideroflexin 3 (SFXN3) as a possible prognostic biomarker in AML by integrating transcriptome and survival data from the TCGA and GTEx databases. Clinical correlation analysis revealed a strong association between increased SFXN3 expression and both advanced age and poor overall survival. Stratified survival analyses confirmed the predictive value of the model across multiple clinical subgroups. It has been demonstrated through the implementation of functional assays that SFXN3 exerts a pivotal role in the promotion of AML cell proliferation and the suppression of apoptosis. This function is primarily attributed to the activation of the Wnt/β-Catenin signaling pathway. Mechanistically, the transcription factor REST was identified as a direct upstream regulator of SFXN3, capable of binding to its promoter region and transcriptionally activating it. The present study has identified the REST-SFXN3-Wnt/β-Catenin axis as a critical regulator of AML cell growth and survival. Furthermore, pharmacological experiments revealed that SFXN3 knockdown significantly enhanced AML cell sensitivity to decitabine, suggesting that co-targeting SFXN3 could improve chemotherapeutic efficacy and help overcome drug resistance. This research provides a comprehensive clarification of the role of SFXN3 in AML, its biological function, and its upstream regulation. Furthermore, the present study unveils a novel signaling pathway involving REST-SFXN3-Wnt/β-Catenin, which may serve as a therapeutic target. These results provide a valuable insight into the underlying causes of AML and offer a potential framework for precision therapy approaches.
A review of treatment strategies for elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia.
Shi K, Wang G, Sun X
Transl Oncol · 2026 Apr · PMID 41690286 · Full text
The treatment of elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (pH⁻ B-ALL) remains challenging because of the high frequency of adverse genetic features, common comorbidities,...
The treatment of elderly patients with Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia (pH⁻ B-ALL) remains challenging because of the high frequency of adverse genetic features, common comorbidities, and significant treatment-related toxicities, which collectively limit the efficacy of conventional chemotherapy and result in poor long-term survival. Recent years have witnessed the emergence of novel targeted agents and immunotherapies, substantially improving the therapeutic outlook for this population. This review summarizes recent advances in the application of low-intensity chemotherapy, CD19/CD22-targeting antibodies such as blinatumomab and inotuzumab ozogamicin, the BCL-2 inhibitor venetoclax, and chimeric antigen receptor (CAR) T-cell therapy for elderly pH⁻ B-ALL patients. Clinical studies indicate that these strategies can increase remission rates and survival while reducing treatment-related toxicity, offering particular benefit to older patients who are unsuitable for intensive chemotherapy. Future efforts should focus on optimizing combination and sequential regimens, as well as personalizing treatment approaches to further improve efficacy and safety.
Imaging-guided optimization of biodistribution and antitumor efficacy of L19-based immunocytokines.
Virgilio T, Chahine K, Carreras JG … +10 more , Pulfer A, Pizzichetti C, Latino I, Molina-Romero D, Capucetti A, Renner LL, Neri D, Puca E, De Luca R, Gonzalez SF
Transl Oncol · 2026 Apr · PMID 41690285 · Full text
Antibody-based targeted delivery of pharmaceuticals is an attractive approach to preferentially localize anti-cancer payloads to neoplastic lesions. The L19 antibody, specific for the extra domain B of fibronectin, is us...
Antibody-based targeted delivery of pharmaceuticals is an attractive approach to preferentially localize anti-cancer payloads to neoplastic lesions. The L19 antibody, specific for the extra domain B of fibronectin, is used in several antibody-cytokine fusion proteins investigated in clinical trials involving different tumor types. However, improving the efficacy of L19-based immunotherapies requires a detailed understanding of how delivery strategies influence intratumoral distribution and therapeutic outcomes. In this study, we investigate the biodistribution of the L19 antibody in murine models of primary Eμ-myc lymphoma and metastatic MC38 colon carcinoma. Using high-resolution in vivo and ex vivo microscopy, we compared subcutaneous (s.c.) and intravenous (i.v.) administration of L19, revealing rapid accumulation in tumor invaded lymph nodes within 10-30 min post injection. While both routes enabled initial tumor targeting, i.v. injection led to longer retention (up to 72 h) and greater selectivity for tumor associated blood vasculature. In contrast, s.c. delivery favored transient accumulation near lymphatic vessels and exhibited reduced tumor residence. These distribution patterns directly influenced the therapeutic efficacy of the L19-IL2 immunocytokine, which showed superior tumor control following i.v. administration in the MC38 model, consistent with enhanced blood vascularization in this model. Our findings demonstrate that L19 binds both blood and lymphatic vasculature in primary and metastatic disease, underscoring the critical impact of the administration route on antibody biodistribution, microanatomical localization, and therapeutic outcome. Moreover, this work highlights the utility of microscopy guided analysis in optimizing delivery strategies and supports the rationale for tailoring administration routes based on tumor type and vascular context in antibody-based theranostics.
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