Translational Oncology[JOURNAL]
Sun
200 papers
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.
Encapsulation of hydroxyurea in exosomes derived from adipose mesenchymal stem cells enhances anticancer efficacy in breast cancer.
Taheri Kangarshahi Z, Ganji SM, Ashrafi F … +1 more , Abbasi A
Transl Oncol · 2026 Apr · PMID 41702234 · Full text
Breast cancer treatment faces numerous challenges, including drug resistance and lack of precise drug targeting, which reduce therapeutic efficacy. This study investigated the potential use of hydroxyurea (HU), a potent...
Breast cancer treatment faces numerous challenges, including drug resistance and lack of precise drug targeting, which reduce therapeutic efficacy. This study investigated the potential use of hydroxyurea (HU), a potent antimetabolite, and exosomes derived from adipose-derived mesenchymal stem cells (AD-MSCs) as natural drug carriers to improve breast cancer therapy. Exosomes were isolated from AD-MSCs and characterized using immunophenotyping and various analytical techniques. HU was subsequently loaded into the exosomes via sonication, and its concentration was quantified by high-performance liquid chromatography (HPLC). Anticancer effects were evaluated through cell viability assays, apoptosis analysis, cell cycle profiling, and real-time PCR assessment of genes related to metastasis and angiogenesis. HU-loaded exosomes (HU-Exo) significantly enhanced cytotoxicity, reducing the IC50 value by up to threefold compared to free HU. HU-Exo also promoted apoptosis, induced S-phase cell cycle arrest, and inhibited migration of 4T1 breast cancer cells. Furthermore, expression of MMP2, MMP9, and VEGF was markedly downregulated. These results suggest that exosomes improve drug uptake and bypass drug resistance mechanisms, enabling dose reduction and minimizing side effects. This study introduces HU-Exo as a targeted and multifaceted drug delivery system capable of inhibiting breast tumor growth and metastasis, paving the way for the development of novel and combination therapies in the future.
Clinicopathological and functional evaluation of replication protein A in epithelial ovarian cancers: A target validation study.
Algethami M, Sheha A, Singhania N … +11 more , Alqahtani S, Shoqafi A, Tosun Ç, Spicer J, Toss MS, Alblihy A, Lashen A, Jeyapalan JN, Mongan NP, Rakha EA, Madhusudan S
Transl Oncol · 2026 Apr · PMID 41702233 · Full text
Replication Protein A (RPA), a single-stranded DNA (ssDNA)-binding protein is critically involved in DNA replication, checkpoint regulation and DNA repair. We evaluated RPA1, 2, and 3 sub-units protein expression in 331...
Replication Protein A (RPA), a single-stranded DNA (ssDNA)-binding protein is critically involved in DNA replication, checkpoint regulation and DNA repair. We evaluated RPA1, 2, and 3 sub-units protein expression in 331 ovarian tumours, transcripts in 1287 tumours and bioinformatics in the ovarian TCGA cohort (n = 379). Platinum resistant ovarian cancer cells were depleted for RPA 1 or 2 and tested for cisplatin, olaparib and talazoparib sensitivity. HAMNO (RPA1 protein-protein interaction inhibitor) was tested in sensitive and resistant cells. High nuclear RPA1 and RPA2 protein was significantly associated with high grade serous ovarian cancers (HGSOC), advanced stage, platinum resistance and worse progression free survival (PFS) (all ps <0.05). High RPA1 and RPA2 transcripts also linked with poor PFS. Preclinically, RPA1 or RPA 2 depletion increased sensitivity to cisplatin, olaparib and talazoparib treatment. HAMNO monotherapy was cytotoxic to sensitive and resistant cells. We conclude that RPA directed precision oncology strategy could be a viable strategy in HGSOC.
Integrative bioinformatics identifies NSCLC biomarkers associated with LPS metabolism and circadian disruption.
Chen Y, Zhao Y, Kong Q … +3 more , Li Y, Jiang P, Fan L
Transl Oncol · 2026 Apr · PMID 41691850 · Full text
PURPOSE: Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer-related mortality worldwide, highlighting the urgent need for early detection and targeted therapies. While lipopolysaccharide (LPS) metabolism...
PURPOSE: Non-small cell lung carcinoma (NSCLC) is a leading cause of cancer-related mortality worldwide, highlighting the urgent need for early detection and targeted therapies. While lipopolysaccharide (LPS) metabolism and circadian rhythm disruption are emerging as important factors in cancer progression, their specific roles in NSCLC remain poorly understood. METHODS: We integrated multiple GEO datasets to identify NSCLC-associated differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) identified key gene modules, followed by functional enrichment analysis. A hybrid machine learning approach combining Lasso regression and random forest was used to identify hub genes. Immune infiltration analysis evaluated associations with the tumor microenvironment, and diagnostic performance was validated in an independent cohort. Functional roles of the candidate gene CACNA2D2 were assessed through gain- and loss-of-function experiments in A549 cells, evaluating viability, proliferation, migration, and invasion. RESULTS: We identified 889 significant DEGs enriched in inflammatory and immune-related pathways. WGCNA revealed the magenta module as highly associated with NSCLC, involved in angiogenesis and extracellular matrix organization. Machine learning identified nine hub genes (CACNA2D2, ASPA, LRRN3, ABCA6, TNFSF12, AHNAK, TACC1, ID4, TSLP) showing excellent diagnostic performance (AUC: 0.832-0.906). These genes correlated significantly with immune cell infiltration patterns. Functional validation established CACNA2D2 as a tumor suppressor, where its depletion enhanced malignant phenotypes while overexpression suppressed them. CONCLUSION: This study identifies a novel gene signature linked to LPS metabolism and circadian disruption in NSCLC, with validated diagnostic utility and implications for tumor immune regulation. CACNA2D2 emerges as a key tumor suppressor, offering insights for early detection and targeted therapy development.
The VAX2-SERPINE1 axis modulates colorectal cancer cell proliferation and apoptosis through WNT/beta-catenin signaling.
Zhang J, Liu G, Peng S … +16 more , Chen Y, Xie Y, Lei Y, Wu J, Huang X, Wei X, Hong L, Yang P, Peng Y, Tang W, Wu X, Li A, Liu S, Shi X, Xiong J, Wang J
Transl Oncol · 2026 Apr · PMID 41691849 · Full text
Transcription factors (TFs) involve in colorectal cancer (CRC). However, the function and mechanism of VAX2 in the development of CRC remain barely known. In the present study, we observed that transcription factor VAX2...
Transcription factors (TFs) involve in colorectal cancer (CRC). However, the function and mechanism of VAX2 in the development of CRC remain barely known. In the present study, we observed that transcription factor VAX2 is frequently upregulated in CRC internal sample set and external tissue microarray and cell lines. High VAX2 expression is observably correlated with tumor invasiveness and AJCC stage of tumors in CRC. Furthermore, decreased expression of VAX2 functionally inhibits the proliferation and facilitates the apoptosis of CRC cells and vice versa. Mechanistically, VAX2 involves in WNT/beta-catenin signaling through facilitating the nucleus accumulation of beta-catenin and VAX2 specifically binds to the promoter and trigger the transcription of SERPINE1. SERPINE1 overexpression significantly reverses the suppression of malignant behavior and nucleus accumulation of beta-catenin induced by VAX2 knockdown in vitro. In vivo, both the knockdown of SERPINE1 and the oral administration of its inhibitor Tiplaxtinin consistently attenuated the VAX2-enhanced proliferative capacity. Consistent with analysis of TCGA-CRC, positive correlation can be detected between VAX2 and SERPINE1 in fresh CRC samples. Thus, VAX2-SERPINE1 axis participate in CRC progression and work as a potential target against CRC.
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.
FOSL1 promotes homologous recombination repair and camptothecin resistance via TCOF1-mediated ribosome biogenesis in non-small cell lung cancer.
Hao C, Chen L, Liao F … +3 more , Chen L, Yao Y, Song Q
Transl Oncol · 2026 Apr · PMID 41687404 · Full text
BACKGROUND: Camptothecin (CPT) and its derivatives are important chemotherapeutic agents; however, intrinsic and acquired tolerance frequently limits their long-term efficacy. This study aimed to identify key transcripti...
BACKGROUND: Camptothecin (CPT) and its derivatives are important chemotherapeutic agents; however, intrinsic and acquired tolerance frequently limits their long-term efficacy. This study aimed to identify key transcriptional regulators of CPT responsiveness in non-small cell lung cancer (NSCLC) and to elucidate the underlying molecular mechanisms. METHODS: Single-cell RNA sequencing-based transcriptomic profiling, integrated with bulk RNA-seq, was used to prioritize CPT-responsive transcriptional programs and nominate candidate regulators. Functional roles were validated using gain- and loss-of-function approaches in NSCLC cell lines. DNA damage repair, ribosome biogenesis, and translational activity were assessed using molecular and reporter assays. Pharmacological inhibition of ribosome biogenesis was evaluated using the RNA polymerase I inhibitor BMH-21, and therapeutic relevance was further examined in xenograft models. RESULTS: We identified FOSL1 as a CPT-responsive transcription factor that was associated with poor prognosis in lung adenocarcinoma. CPT treatment induced FOSL1 expression and nuclear accumulation, whereas FOSL1 depletion markedly enhanced CPT-induced cytotoxicity. Mechanistically, loss of FOSL1 resulted in persistent DNA damage accumulation and selective impairment of homologous recombination (HR) repair. FOSL1 sustained HR repair indirectly by promoting ribosome biogenesis through transcriptional activation of TCOF1. Pharmacological inhibition of ribosome biogenesis phenocopied FOSL1 depletion and significantly potentiated CPT efficacy both in vitro and in vivo. CONCLUSION: Our study defines a FOSL1-TCOF1-ribosome axis that promotes CPT tolerance in NSCLC by maintaining HR repair. These findings provide a rationale for targeting ribosome biogenesis to enhance CPT-based treatment and highlight coordinated regulation of transcription, protein synthesis, and DNA repair under chemotherapeutic stress.
OSBPL3 promotes LUAD metastasis and glycolysis through transcriptional upregulation of PLAU via NFE2L2.
Zhang Q, Zhang J, Li J … +4 more , Chen S, Liu Y, Li K, Guo M
Transl Oncol · 2026 Apr · PMID 41687403 · Full text
The progression of lung adenocarcinoma (LUAD) involves multiple molecular determinants, among which Oxysterol-binding protein-like 3 (OSBPL3) has been suggested to contribute to tumorigenesis, though its functional signi...
The progression of lung adenocarcinoma (LUAD) involves multiple molecular determinants, among which Oxysterol-binding protein-like 3 (OSBPL3) has been suggested to contribute to tumorigenesis, though its functional significance in LUAD remains poorly characterized. In this study, we elucidate the oncogenic functions and underlying mechanisms of OSBPL3 in LUAD pathogenesis. Analysis of clinical specimens revealed upregulated OSBPL3 expression in LUAD, which correlated with unfavorable patient outcomes. Genetic depletion of OSBPL3 in vitro impeded cellular proliferation, migratory capacity, and cell cycle progression, while inducing apoptotic cell death. Mechanistically, OSBPL3 was found to interact with the transcription factor NFE2L2, promoting its nuclear translocation and enhancing the transcriptional activation of PLAU, a downstream target gene. Upregulation of PLAU subsequently stimulated expression of key glycolytic enzymes through PI3K/AKT pathway activation, resulting in increased glucose consumption and lactate secretion. This metabolic reprogramming toward aerobic glycolysis facilitated malignant progression. Both genetic inhibition of PLAU and pharmacological blockade of AKT signaling abrogated the tumor-promoting phenotypes induced by OSBPL3. In vivo, OSBPL3 silencing significantly attenuated tumor growth and promoted apoptosis. Collectively, these findings identify an OSBPL3-NFE2L2-PLAU-AKT signaling axis that drives glycolytic metabolism and LUAD progression, showing its potential as a therapeutic target.
An unfavorable biologic profile associated with decreased overall survival and cancer-specific survival in non-metastatic breast cancer: A latent class analysis.
Falandry C, Hatse S, Brouwers B … +7 more , Kenis C, Smeets A, Neven P, Cuerq C, Pamoukdjian F, Chikh K, Wildiers H
Transl Oncol · 2026 Apr · PMID 41687402 · Full text
BACKGROUND: Chronological age is an imperfect proxy for risk assessment in geriatric oncology. There is an urgent need for an objective, easily measurable biological aging signature to refine patient stratification and p...
BACKGROUND: Chronological age is an imperfect proxy for risk assessment in geriatric oncology. There is an urgent need for an objective, easily measurable biological aging signature to refine patient stratification and personalize therapeutic decisions. METHODS: We analyzed a panel of seven aging-related biomarkers (including markers of inflammation, anabolic reserve, and telomere status) in 244 nonmetastatic breast cancer patients from two age groups ("Old", ≥70 years, N = 162; "Young", ≤60 years, N = 82). We used Latent Class Analysis (LCA) to integrate these markers and identify distinct biological risk profiles. These profiles were then evaluated for their association with Overall Survival (OS) and Cancer-Specific Death (CSD) via Competing Risk Analysis. RESULTS: LCA identified two patient profiles. The Unfavorable Biologic Profile (56.1% of the cohort) was defined by a triad of high MCP-1, high Chitinase activity, and low IGF-1. This profile was strongly associated with poorer OS (Age-adjusted HR=1.82, p = 0.018). Crucially, 15% of chronologically "Young" patients were assigned to this high-risk profile, while 23% of "Old" patients were assigned to the Favorable Profile. Furthermore, the Unfavorable Profile was more strongly and specifically associated with CSD (Subdistribution HR: 2.05, p = 0.012) than with Non-Cancer Death. CONCLUSION: Our results delineate an unfavorable, trans-chronological biological profile that identifies patients with low host reserve, largely driven by inflammaging and catabolism. This integrated signature provides a robust, objective screening tool to identify biologically frail patients, validating the need for Comprehensive Geriatric Assessment (CGA) and biomarker-guided therapeutic de-escalation (e.g., avoiding adjuvant chemotherapy) to improve individualized outcomes in oncology. TRIAL REGISTRATION: BS32220096117.
Piperlongumine suppresses YAP-ET-1-CXCL2 signaling to modulates aggressiveness of triple-negative breast cancer cells.
Hsieh MY, Yang CC, Hsu WJ … +7 more , Liu ZW, Lu HY, Chiang MC, Huang CJ, Liao CY, Lin CW, Shueng PW
Transl Oncol · 2026 Apr · PMID 41687401 · Full text
Triple-negative breast cancer (TNBC) is characterized by highly aggressive and metastatic properties, and appropriate molecular targets and therapeutics for effective treatment remain limited. In the present study, by us...
Triple-negative breast cancer (TNBC) is characterized by highly aggressive and metastatic properties, and appropriate molecular targets and therapeutics for effective treatment remain limited. In the present study, by using RNA sequencing (RNA-Seq) analysis of upregulated genes expression in metastatic breast tumor cells, we identified that the Yes-associated protein (YAP)- endothelin (ET)-1 signaling axis were concomitantly elevated in metastatic breast tumor tissues and their overexpression conferred poor survival outcomes, particular in patients with TNBC. Moreover, we identified that piperlongumine (PL), a naturally occurring small molecule derived from long pepper, exhibits potent antitumor activities in TNBC cells. PL effectively suppressed cell proliferation, promoted apoptosis, and inhibited tumor migration and invasion. Furthermore, PL activates Hippo signaling which was accompanied by downregulation of YAP level. Consequently, PL suppressed YAP signaling to further downregulate ET-1 expression. Additionally, ET-1 elevation was identified to be associated with cancer-associated fibroblast (CAF) and C-X-C motif chemokine ligand 2 (CXCL2) signature, while treatment with PL significantly downregulated CXCL2 expression and consequently decreased CAF activation. Finally, PL treatment significantly inhibited in vivo tumor growth and suppressed CAF infiltration in the tumor microenvironment. Together, these findings demonstrated that PL might be a promising chemotherapeutic agent to efficiently target YAP-ET-1-CXCL2 signaling and thus has therapeutic potential for TNBC patients.
The novel tertiary amine LSD1 inhibitor 596 inhibits endometrial cancer through the mTOR signal transduction pathway.
Wang C, Shen D, Lin N … +7 more , Wang P, Bi Y, Hu H, Shang Y, Ren C, Yang L, Ma Q
Transl Oncol · 2026 Apr · PMID 41671780 · Full text
Lysine-specific demethylase 1 (LSD1) is a promising target in cancer therapy and plays an important role in the occurrence and development of tumors. However, research on LSD1 in endometrial cancer (EC) is indeed limited...
Lysine-specific demethylase 1 (LSD1) is a promising target in cancer therapy and plays an important role in the occurrence and development of tumors. However, research on LSD1 in endometrial cancer (EC) is indeed limited, and the related research on LSD1 inhibitors targeting EC is even rarer. In this study, our group developed a novel Tertiary Amine LSD1 inhibitor-596. 596 could specifically target LSD1 and inhibit the demethylation levels of H3K4me1/2 in a dose-dependent manner, thereby inhibited the proliferation of EC cells in vitro and in vivo. Moreover, in-depth studies have shown that 596 induces cell death in EC cells through the autophagy pathway, increasing the formation of autophagosomes and the expression of autophagy-related proteins. Transcriptomic sequencing revealed that 596-induced gene enrichment was related to the PI3K/AKT/mTOR pathway. The treatment group of 596 was able to attenuate the activation of the mTOR signaling cascade, and the combination treatment of 596 and the mTOR inhibitor rapamycin (RAPA) effectively reduced the survival rate, migration ability, and invasion ability of EC cells. Further studies in vitro and in vivo indicated that 596 could reduce the feedback activation of AKT mediated by the mTOR inhibitor rapamycin. In summary, our findings demonstrate that the LSD1 inhibitor 596 enhances the activity of the mTOR inhibitor by attenuating the feedback activation of AKT. LSD1 may be as a potential therapeutic target in EC, and LSD1 inhibitors represent an important therapeutic strategy in EC treatment.
Multi-omics analysis of NET+ TAN explains the immunosuppressive TME and prognosis value of malignant clinical characteristics in TNBC.
Zhu Q, Zheng X, Zhu X … +2 more , Yang P, Yang M
Transl Oncol · 2026 Apr · PMID 41671779 · Full text
Triple-negative breast cancer (TNBC) continues to exhibit a poor response to both immunotherapy and endocrine therapy, primarily due to its complex genetic heterogeneity and tumor immune microenvironment (TIME). Neutroph...
Triple-negative breast cancer (TNBC) continues to exhibit a poor response to both immunotherapy and endocrine therapy, primarily due to its complex genetic heterogeneity and tumor immune microenvironment (TIME). Neutrophil extracellular traps (NETs) are involved in neutrophil development and degranulation in treatment-resistant tumors, particularly TNBC and metastatic cases. Using a combination of single-cell RNA sequencing (scRNA-seq) datasets, bulk mRNA sequencing data from The Cancer Genome Atlas (TCGA) cohort, microarray data from the METABRIC and GEO databases, and epigenetic sequencing resources, we comprehensively investigated the functional characteristics and prognostic potential of NET-positive tumor-associated neutrophils (NET+ TAN) in TNBC. A six-gene panel derived from NET+ TAN has been identified as a reliable diagnostic biomarker for the survival of patients with TNBC and has been validated across several independent cohorts. Notably, our findings indicate that NET+ TAN facilitate T cell reprogramming in TNBC, thereby establishing a suppressive TIME and promoting tumor progression. This study provides a comprehensive perspective on the significance of NETs in patients with TNBC, with the aim of offering genetic and epigenetic insights into the mechanisms by which NETs may transition from cold to hot tumor phenotype, as well as valuable recommendations for therapeutic strategies.
Overcoming the leptomeningeal seeding of medulloblastoma by targeting HSP70.
Choi SA, Heng S, Ha S … +4 more , Kim SK, Hwang DW, Youn H, Phi JH
Transl Oncol · 2026 Apr · PMID 41666663 · Full text
Leptomeningeal seeding (LMS) via cerebrospinal fluid is a common and often fatal progression in medulloblastoma (MB), significantly worsening prognosis. However, its molecular drivers are poorly understood, and effective...
Leptomeningeal seeding (LMS) via cerebrospinal fluid is a common and often fatal progression in medulloblastoma (MB), significantly worsening prognosis. However, its molecular drivers are poorly understood, and effective treatments remain limited. This study aimed to establish a physiologically relevant MB LMS model and identify novel therapeutic targets through detailed characterization of seeding cell biology. Using three rounds of serial orthotopic xenograft transplantation and in vivo selection, we isolated distinct seeding (S3) and non-seeding (N3) MB cell populations. Functional and transcriptomic analyses revealed unique phenotypes and differentially expressed genes (DEGs). Based on DEGs, we screened inhibitors and assessed the therapeutic efficacy of the HSP70 inhibitor VER155008, alone and with chemotherapeutics (ifosfamide or cisplatin), both in vitro and in a preclinical LMS mouse model established by cerebellar implantation of S3 cells. S3 cells showed slower proliferation, altered migration behavior, and increased adhesion to collagen IV versus N3 cells. Transcriptomic profiling identified HSP70 as the most upregulated gene in S3 cells, with strong enrichment in metabolic pathways. Among six candidate compounds, VER155008 most effectively suppressed S3 cell viability. In vitro, VER155008 combined with 4-hydroperoxycyclophosphamide (active ifosfamide metabolite) produced a synergistic antitumor effect. This synergy was confirmed in vivo, where VER155008 with ifosfamide significantly reduced spinal LMS. These findings highlight HSP70 as a promising therapeutic target for MB LMS. The observed synergy between VER155008 and ifosfamide supports a selective combination strategy, offering a novel therapeutic avenue to improve outcomes in patients with leptomeningeal dissemination of MB.
SPP1⁺ macrophage-FADS1⁺ tumor cell crosstalk via the PDGFB-PDGFRB axis drives liver metastasis in colorectal cancer.
Zhao P, Pei F, Liu Y … +7 more , Jiang Y, Fang X, Shu L, Hu X, Chen F, Feng M, Li X
Transl Oncol · 2026 Apr · PMID 41655559 · Full text
Liver metastasis is the predominant cause of mortality among individuals diagnosed with colorectal cancer (CRC). However, the mechanisms underlying the tumor-microenvironment interactions that promote this process remain...
Liver metastasis is the predominant cause of mortality among individuals diagnosed with colorectal cancer (CRC). However, the mechanisms underlying the tumor-microenvironment interactions that promote this process remain poorly defined. Here, we developed an integrative multiomics framework to dissect the cellular and molecular determinants of colorectal cancer liver metastasis (CRLM). By analyzing 1,156 metastasis-associated genes, we identified three molecular subtypes with distinct prognostic and immunometabolic features: C1 with mixed phenotypes and favorable survival, C2 with metabolic activation and immune suppression, and C3 with immune activation and signaling dysregulation, which had the poorest outcomes. Mechanistically, we discovered that SPP1⁺ macrophages secrete PDGFB, which activates PDGFRB signaling in FADS1⁺ tumor cells to trigger epithelial-mesenchymal transition (EMT) and promote liver metastasis. This macrophage-tumor crosstalk was validated by single-cell transcriptomics, genetic perturbation, and coculture experiments. Collectively, our findings define a macrophage-derived PDGFB-PDGFRB axis that drives CRC liver metastasis and highlight a potential therapeutic target for overcoming metastatic progression and immune resistance.
Application of radiomics in head and neck squamous cell carcinoma.
Wu S, Wang Z, Zhang Y … +6 more , Chen Q, Liu H, Shen Y, Xiao J, Zhao L, Mao Y
Transl Oncol · 2026 Apr · PMID 41655558 · Full text
Head and neck squamous cell carcinoma (HNSCC) is the most prevalent histopathological subtype of head and neck malignancies. Owing to the lack of early specific symptoms, the majority of patients are diagnosed at interme...
Head and neck squamous cell carcinoma (HNSCC) is the most prevalent histopathological subtype of head and neck malignancies. Owing to the lack of early specific symptoms, the majority of patients are diagnosed at intermediate or advanced stages, which is associated with an unfavorable prognosis and a substantial decline in quality of life. Radiomics, which leverages large-scale medical imaging data, enables the extraction of high-dimensional quantitative features through advanced image analysis, thereby providing deeper insights into tumor biology. In this review, we summarize recent advances in radiomics for the diagnosis, prognostic prediction, and evaluation of treatment-related toxicity in HNSCC. Furthermore, we highlight emerging applications of radiomics in genomics and proteomics, illustrating the associations between tumor molecular phenotypes and imaging-derived features. Finally, we discuss the challenges related to feature standardization and reproducibility, and outline the key limitations of current radiomics studies.
Development and validation of prognostic nomograms based on peripheral blood T-cell counts and their dynamic changes for patients with nasopharyngeal carcinoma receiving radiotherapy.
Weng K, Lei Q, Hong Y … +4 more , Chen K, Sun Y, Wang Y, Zhu X
Transl Oncol · 2026 Apr · PMID 41655557 · Full text
AIM: To develop and validate prognostic nomograms incorporating peripheral blood lymphocyte counts and their dynamic changes in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. METHODS: In this retro...
AIM: To develop and validate prognostic nomograms incorporating peripheral blood lymphocyte counts and their dynamic changes in patients with nasopharyngeal carcinoma (NPC) undergoing radiotherapy. METHODS: In this retrospective cohort study, consecutive patients with NPC who received radiotherapy at Chongqing University Cancer Hospital were included as the internal cohort (randomly divided 70 %/30 % for training and validation), while patients treated at Guangxi Medical University Cancer Hospital served as the external validation cohort. Prognostic nomograms for progression-free survival (PFS) and overall survival (OS) were constructed using multivariable Cox regression analyses. RESULTS: The internal and external cohorts comprised 746 and 138 patients, respectively. Age, gross tumor volume dose, neoadjuvant chemotherapy, clinical stage, plasma EBV-DNA level, baseline total T-cell count, and its post-treatment change (ΔT cells) were identified as independent prognostic factors. The nomograms demonstrated strong predictive performance, with concordance indices of 0.701, 0.716, and 0.714 for PFS, and 0.759, 0.735, and 0.734 for OS in the training, internal validation, and external datasets, respectively. The areas under the receiver operating characteristic curves for 3-year and 5-year PFS and OS exceeded 0.7 across all cohorts. Calibration plots indicated good agreement between predicted and observed outcomes, and decision curve analysis confirmed greater net clinical benefit compared with TNM staging and EBV-DNA-based models. CONCLUSION: The proposed T-cell-based nomograms reliably predict PFS and OS in patients with NPC undergoing radiotherapy and were validated in an external cohort. These models provide improved prognostic discrimination beyond conventional staging systems and may assist in individualized risk stratification and management planning.
CMS subtypes correlate with complete response in trial of neoadjuvant Galunisertib plus chemoradiation in rectal cancer.
Rajamanickam V, Simons ND, Rosales W … +17 more , Kravchenko A, Yamazaki T, Bernard B, Piening B, Domingo E, Maughan T, Alvarez-Jimenez C, Desilvio T, Viswanath S, Whiteford M, Hayman A, O'Brien D, Kiely MX, Ahmad R, Gough MJ, Crittenden MR, Young KH
Transl Oncol · 2026 Apr · PMID 41653703 · Full text
Improving responses to neoadjuvant therapy for patients with locally advanced rectal cancer has the potential to improve organ preservation and disease-free survival. Knowing which patients may need therapeutic escalatio...
Improving responses to neoadjuvant therapy for patients with locally advanced rectal cancer has the potential to improve organ preservation and disease-free survival. Knowing which patients may need therapeutic escalation or de-escalation from standard-of-care treatment remains an area of investigation. We previously reported the primary and secondary endpoints of our single-arm study combining transforming growth factor beta receptor inhibitor, Galunisertib, with neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Here we analyze RNA sequencing data obtained from tissue biopsies at baseline and after 2 weeks of galunisertib. Differences in expression of genes associated with MYC, inflammation, and epithelial-to-mesenchymal transition were observed between complete responders (CR) and <CR, with galunisertib upregulating MYC pathway expression in CR. Radiosensitivity and TGFβ response scores demonstrated limited ability to predict for response to galunisertib + chemoradiation. Typically treatment-resistant consensus molecular subtype 4 (CMS4), characterized by TGFβ expression, and metabolic subtype (CMS3) were associated with response to galunisertib + chemoradiation. Differences in correlations between RNA based measures of cell composition and immunohistologic quantification of infiltrates and extracted MRI parameters were observed for CIBERSORT, MCPcounter, and xCell methodologies. Based on these data, we hypothesize that the stromal radioresistant phenotype driven by TGFβ can be overcome by the addition of galunisertib to chemoradiation in rectal cancer.
Computed tomography- and magnetic resonance imaging-based multi-modality radiomics models for predicting survival in esophageal cancer patients.
Chu F, Li D, Wang Z … +6 more , Bai B, Zhao K, Wang S, Wang C, Yang G, Qu J
Transl Oncol · 2026 Mar · PMID 41650806 · Full text
OBJECTIVES: This study explores the integration of radiomics features from contrast-enhanced CT and MRI with clinical and radiological risk factors for optimal prognosis models of disease-free survival (DFS) and overall...
OBJECTIVES: This study explores the integration of radiomics features from contrast-enhanced CT and MRI with clinical and radiological risk factors for optimal prognosis models of disease-free survival (DFS) and overall survival (OS) in esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: A retrospective study is undertaken of 371 ESCC patients who underwent contrast-enhanced CT and MRI with StarVIBE sequence, from September 2014 to December 2019. Prognosis models for DFS and OS were developed using cross-validation and Elastic-Net-Cox regression. Patients were grouped by treatment type (surgery, chemoradiotherapy, neoadjuvant therapy) to create single-modality and multi-modality models (Model-S, Model-CRT, and Model-nT). Model performance was evaluated using nomograms, calibration curves, and decision curves. RESULTS: Twelve optimal prognosis models were identified. For DFS, MRI c-indices were 0.595, 0.608, and 0.721, while CT c-indices were 0.686, 0.616, and 0.667. For OS, MRI c-indices were 0.692, 0.597, and 0.650, and CT c-indices were 0.656, 0.623, and 0.695. Multi-modality models demonstrated c-indices of 0.750, 0.695, 0.839 for DFS and 0.898, 0.777, 0.819 for OS. CONCLUSION: Single-modality radiomics models exhibit limited predictive ability for DFS and OS in ESCC patients, whereas multi-modality radiomics models enhance predictive accuracy significantly.
Improving photodynamic therapy efficacy in bladder cancer using polymer micelle-encapsulated pheophorbide a.
Labroy M, Chabaud S, Durand M … +4 more , Fourquaux I, Bolduc S, Bordeleau F, Gibot L
Transl Oncol · 2026 Mar · PMID 41650805 · Full text
BACKGROUND: Photodynamic diagnosis (PDD) is widely used in bladder cancer management, enabling fluorescence-guided detection of lesions through intravesical administration of photosensitizers such as hexaminolevulinate (...
BACKGROUND: Photodynamic diagnosis (PDD) is widely used in bladder cancer management, enabling fluorescence-guided detection of lesions through intravesical administration of photosensitizers such as hexaminolevulinate (Cysview®/Hexvix®). Building on this clinical framework, we explored photodynamic therapy (PDT) using pheophorbide a (pheo), a chlorophyll-based photosensitizer, encapsulated in self-assembled poly(ethylene oxide)-block-poly(ε-caprolactone) (PEO-PCL) micelles. RESULTS: In vitro assays were performed on human bladder cancer cell lines, namely the grade 3 invasive T24 and the grade 1 SW780, in both 2D monolayers and 3D spheroid cultures. In 2D, encapsulated pheo showed higher phototoxicity (IC₅₀: 129 nM T24, 156 nM SW780), while free pheo exhibited negligible effects, preventing IC₅₀ determination. Two-photon microscopy confirmed that encapsulation markedly enhanced pheo penetration, especially in T24. SW780 spheroids exhibited tight epithelial features and low permeability, forming characteristic microbladder-like vesicles. PDT reduced viability in both T24 and SW780 3D models, with a significant advantage for encapsulated pheo at day 6 post-treatment in T24 spheroids. Preliminary exploration in human tissue-engineered bladder tumor substitutes demonstrated the feasibility for PDT assessment in complex 3D environments, warranting further study. CONCLUSIONS: These findings support polymer nanocarrier-mediated pheo delivery as a promising therapeutic approach and pave the way for integrated diagnostic-therapeutic strategies using existing intravesical platforms.
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