Journal Of Cancer Research And Clinical Oncology[JOURNAL]
Sun
200 papers
OLFM4 orchestrates the immunosuppressive microenvironment and drives gallbladder cancer progression.
Li W, Liu K, Yang F … +2 more , He H, Wen W
J Cancer Res Clin Oncol · 2026 Apr · PMID 41934482 · Full text
PURPOSE: Gallbladder cancer (GBC) is the most common biliary tract malignancy, characterized by complex microenvironment and poor prognosis. Olfactomedin-4 (OLFM4) has been identified as a key regulator of GBC progressio...
PURPOSE: Gallbladder cancer (GBC) is the most common biliary tract malignancy, characterized by complex microenvironment and poor prognosis. Olfactomedin-4 (OLFM4) has been identified as a key regulator of GBC progression. This study aims to comprehensively elucidate the molecular profiling, tumor microenvironment (TME) and underlying mechanisms through which OLFM4 drives GBC progression. METHODS: Single-cell RNA sequencing (scRNA-seq) was performed on tumor tissues and adjacent non-tumor tissues (ANT) from clinical GBC samples. We analyzed scRNA-seq data to characterize the landscape of heterogeneous TME and intricate intercellular communication networks of the single cells within GBC. Findings were validated through in vitro experiments. RESULTS: Compared with ANT, GBC exhibited a distinct remodeling of the tumor microenvironment. Specifically, epithelial cells were markedly enriched in GBC (18.2% vs. 11.6% in ANT), accompanied by a pronounced reduction in endothelial cells (2.4% vs. 9.7%). In parallel, myeloid cells decreased from 16.8% in ANT to 11.5% in GBC, while fibroblasts remained comparably abundant in both conditions (21.1%). Within the OLFM4+epithelium, there was a significant enrichment of genes and pathways related to malignant progression, including signatures driving cell proliferation, stemness maintenance (WNT/β-catenin), and metastasis, as well as crucial molecules involved in TME remodeling (SPP1, TGF-β). Pseudotemporal trajectory analysis revealed an upregulation of OLFM4 expression correlating with disease progression, suggesting its close association with malignant transition. Cell-cell communication analysis identified OLFM4+epithelial cells as central signaling hubs, primarily communicating with stromal and immune cells via the SPP1-CD44 and SPP1-Integrin axes. Importantly, OLFM4 knockdown inhibited cell proliferation, migration, invasion, and gemcitabine chemoresistance in vitro, underscoring its central role in GBC progression. CONCLUSION: These findings offer a comprehensive insight into the atlas of molecular signatures and TME within GBC, identifying OLFM4 as a potential biomarker and therapeutic target for GBC.
Improving the diagnosis of renal tumours of young people through integrated molecular analysis.
Leiter SM, Guobadia AO, Fleming B … +24 more , Ajithkumar TV, Armitage JN, Burke GAA, Burns CM, Coleman N, Hatcher H, Horan G, Long AM, McDonald S, Mitchell TJ, Nicholson JC, Roberts T, Stewart GD, Tadross JA, Tarpey PS, Trayers C, Trotman J, Watkins JA, Warren AY, Vujanic GM, Armstrong R, Behjati S, Hook CE, Murray MJ
J Cancer Res Clin Oncol · 2026 Apr · PMID 41933220 · Full text
BACKGROUND: Renal tumours account for one in twenty paediatric cancers, with Wilms tumour (WT) the most common in young children and renal cell carcinoma (RCC) predominating in adolescents and young adults. Diagnostic wo...
BACKGROUND: Renal tumours account for one in twenty paediatric cancers, with Wilms tumour (WT) the most common in young children and renal cell carcinoma (RCC) predominating in adolescents and young adults. Diagnostic work-up has traditionally focused on clinical features, radiology, and histology, with a limited role for molecular analysis. However, it is estimated that up to one-third of children with WT have underlying cancer predisposition, which could necessitate prolonged treatment and intensive follow-up. METHODS: Here we describe five children and young adults treated at a single regional centre in England who had paired tumour and germline whole genome sequencing (WGS) as part of their routine diagnostic work-up. RESULTS: One child diagnosed radiologically with a WT underwent pre-operative chemotherapy with good clinical and imaging response. Histological examination of the resection raised concerns over RCC; however, WGS was able to confirm that this was a WT with pathognomonic somatic WT changes. A young adult with upfront nephrectomy had a difficult-to-classify tumour; WGS revealed a novel ERC1-CCNY fusion as a likely novel driver event. Two further children, who did not meet clinical criteria for cancer predisposition testing, had predisposition syndromes identified via agnostic WGS. Finally, a child with piebaldism had a WT-associated REST deletion identified early through critical clinical thinking and expedited microarray. CONCLUSION: We highlight that molecular analysis, particularly agnostic WGS, has a key routine role in the care of children with renal tumours. It is likely that outcomes for these young people have been improved through more accurate diagnosis and early detection of cancer predisposition.
Precision cancer medicine in Europe: a mixed-methods study on infrastructure for extended molecular diagnostics.
Henkel PS, Pedersen K, Taskén K … +6 more , Hult EH, Gelderblom H, Fagereng GL, Landsverk HB, Aas E, PCM4EU consortium partners
J Cancer Res Clin Oncol · 2026 Apr · PMID 41927843 · Full text
PURPOSE: Precision cancer medicine (PCM), targeting cancer treatment to patients' individual genomic profiles, has the potential to improve diagnosis and outcomes substantially. Implementing PCM in healthcare systems req...
PURPOSE: Precision cancer medicine (PCM), targeting cancer treatment to patients' individual genomic profiles, has the potential to improve diagnosis and outcomes substantially. Implementing PCM in healthcare systems requires that extended molecular diagnostics are accessible as part of routine practice. We conducted a mixed-methods study to identify and inform the infrastructure necessary for the implementation of extended molecular diagnostics as part of the health care system. METHODS: To identify and inform relevant categories of necessary infrastructure, we combined a survey, a structured literature search, and expert interviews. The survey included questions on reimbursement and technology assessment of diagnostics for PCM. Findings from the structured literature search were grouped to identify categories of infrastructure together with emerging themes in interviews with experienced oncologists, pathologists, and health technology assessment experts. RESULTS: 44 respondents from 20 countries participated in our survey. We identified and included 45 published papers, and seven experts were interviewed. We identified six key categories for implementing PCM as part of the healthcare system: physical, financial, organisational, competency, data and legal infrastructure. Our combined data sources revealed several themes to promote implementation, including the importance of centralisation of testing, the need for sustainable reimbursement, engagement of relevant stakeholders, interoperability of data infrastructure, and inter-disciplinary collaboration. CONCLUSION: Our results highlight the need for interdisciplinary approaches and the value of initiatives to establish infrastructure within and across countries. While several European countries have come a long way in implementing diagnostics for PCM, considerable work remains to ensure equitable access for patients in need.
Allogeneic CD56 cell-based immunotherapy in a patient with Fanconi anemia developing acute myeloid leukemia.
Dovvombaygi MB, Ghasabeh AS, Eskandarian S … +6 more , Izadpanah A, Safdari SM, Parkhideh S, Seresht-Ahmadi M, Hajifathali A, Roshandel E
J Cancer Res Clin Oncol · 2026 Apr · PMID 41920213 · Full text
BACKGROUND: Fanconi anemia (FA) is a rare inherited disorder characterized by genomic instability, bone marrow failure, and a markedly increased risk of developing acute myeloid leukemia (AML). The intrinsic hypersensiti...
BACKGROUND: Fanconi anemia (FA) is a rare inherited disorder characterized by genomic instability, bone marrow failure, and a markedly increased risk of developing acute myeloid leukemia (AML). The intrinsic hypersensitivity of FA cells to DNA-damaging agents renders conventional chemotherapy particularly toxic and often ineffective. CASE PRESENTATION: A 31-year-old woman with FA who progressed to AML and failed to achieve remission with standard induction therapy. Bone marrow blasts were initially 10%. INTERVENTION: As part of a clinical trial, she received CD56+ cell-based immunotherapy after FLAG chemotherapy. She subsequently underwent allogeneic hematopoietic stem cell transplantation (HSCT) from a matched sibling donor using a CD3+/CD19-depleted graft. Post-transplant, she received additional infusions of CD56+ cells. OUTCOME: CD56+ immunotherapy reduced bone marrow blasts from 10 to 3%, enabling successful HSCT. Post-transplant, she remained in complete remission with no detectable minimal residual disease (MRD) at both day +30 and day +90. CONCLUSION: CD56+ cell-based immunotherapy can effectively decrease the leukemic burden in FA patients with AML, facilitating successful HSCT. This innovative approach may enhance outcomes for high-risk patients and merits further research.
Interventional management of unresectable pancreatic cancer using transarterial chemoembolization and microwave ablation: a single-center evaluation over 12 years.
Vogl TJ, Cojocaru R, Dahm DM … +1 more , Adwan H
J Cancer Res Clin Oncol · 2026 Mar · PMID 41917374 · Full text
PURPOSE: The aim of this study is to evaluate the safety and clinical outcomes of combined transarterial chemoembolization (TACE) and microwave ablation (MWA) as well as TACE monotherapy in patients with unresectable pan...
PURPOSE: The aim of this study is to evaluate the safety and clinical outcomes of combined transarterial chemoembolization (TACE) and microwave ablation (MWA) as well as TACE monotherapy in patients with unresectable pancreatic cancer. MATERIALS AND METHODS: Between 2010 and 2023, 150 patients with unresectable locally advanced pancreatic cancer were included in this retrospective single-center study and treated with either combined TACE and MWA (Group A, n = 67) or TACE alone (Group B, n = 83). In Group A, 23/67 (34.3%) patients presented with metastatic disease and in Group B 45/83 (54.2%) patients had metastatic disease. A total of 222 TACE procedures and 71 MWA procedures were performed in Group A, while 250 TACE procedures were performed in Group B. Follow-up was performed using contrast-enhanced cross-sectional imaging and clinical evaluation. Tumor response and overall survival were analyzed. RESULTS: The mean tumor diameter was 3.4 ± 0.9 cm in Group A and 4.9 ± 1.3 cm in Group B. No major complications occurred in either treatment group. Minor hemorrhage following MWA was observed in 4/71 ablations (5.6%) without further clinical consequence. In Group A, follow-up imaging was available for 47/67 patients, with local tumor progression observed in 5/47 patients (10.6%). The 1-year overall survival rate was 69.4%, with a median overall survival time of 14.6 months (95% CI 12.6–16.7 months). In Group B, follow-up imaging was available for all 83 patients, with local tumor progression observed in 8/83 patients (9.6%). The 1-year overall survival rate was 43.6%, with a median overall survival time of 9.0 months (95% CI 3.3–14.7 months). CONCLUSION: TACE and MWA were safe locoregional treatments for patients with unresectable pancreatic cancer. Both treatment protocols, including the combination of TACE with MWA and TACE as monotherapy, were effective and showed promising results.
CT-based intratumoral, peritumoral radiomics and clinical features: a combined model for perineural invasion prediction in PDAC.
Lan Q, Wang Y, Xia F … +3 more , Sun Y, Cao Y, Wang Z
J Cancer Res Clin Oncol · 2026 Mar · PMID 41902873 · Full text
PURPOSE: To develop and validate a general radiomics nomogram capable of identifying perineural invasion (PNI) status in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: A total of 175 pancreatic cancer patient...
PURPOSE: To develop and validate a general radiomics nomogram capable of identifying perineural invasion (PNI) status in pancreatic ductal adenocarcinoma (PDAC) patients. METHODS: A total of 175 pancreatic cancer patients were retrospectively enrolled in this study. Patients were randomly divided into a training cohort (n = 123) and a test cohort (n = 52) at a ratio of 7:3. Senior physicians manually delineated the intratumoral region of interest (ROI), and the peritumoral ROI was obtained by expanding 3 mm outward from the intratumoral ROI. After extracting and selecting radiomics features, the ExtraTrees algorithm was used to construct intratumoral, peritumoral, and intratumoral + peritumoral radiomics models, respectively. The optimal radiomics model was selected to construct a combined model with clinical characteristics. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the predictive performance of the models. RESULTS: Multivariate analysis showed that carbohydrate antigen 199 (CA199) (p < 0.05) and vascular invasion (p < 0.05) were associated with an increased risk of PNI. In the training cohort, the area under the curve (AUC), sensitivity, and specificity of the combined model were 0.855, 76.8%, and 80.5%, respectively; in the test cohort, they were 0.844, 76.5%, and 77.8%, respectively. The performance of the combined model was superior to that of the clinical model or radiomics model alone. CONCLUSIONS: The combined predictive model integrating intratumoral + peritumoral radiomics features based on contrast-enhanced computed tomography (CE-CT) with clinical characteristics can effectively predict PNI in pancreatic cancer.
Safety and efficacy of nab-paclitaxel combined with nedaplatin and bevacizumab in patients with platinum-resistant epithelial ovarian cancer: a retrospective cohort study.
Li S, Xian B, Cui L … +4 more , Wu L, Fang C, Yang F, Li J
J Cancer Res Clin Oncol · 2026 Mar · PMID 41896491 · Full text
PURPOSE: To evaluate the safety and efficacy of nab-paclitaxel combined with nedaplatin and bevacizumab in patients with platinum-resistant epithelial ovarian cancer (PROC). METHODS: We enrolled PROC patients who receive...
PURPOSE: To evaluate the safety and efficacy of nab-paclitaxel combined with nedaplatin and bevacizumab in patients with platinum-resistant epithelial ovarian cancer (PROC). METHODS: We enrolled PROC patients who received intravenous nab-paclitaxel (260 mg/m), nedaplatin (80 mg/m), and bevacizumab (10 mg/m) every 3 weeks between January 1, 2021, and October 1, 2025. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), CA125 response rate, objective response rate (ORR), duration of response (DOR), and safety. RESULTS: Twenty-seven patients were included (median age 57.8 years; range: 35-78), 16 (59.3%) had received ≥ 3 prior chemotherapy lines; 40.7% and 59.3% had prior bevacizumab and PARP inhibitor exposure, respectively. After a median follow-up of 10 months (range: 3-40), the median PFS was 7.0 months (95% CI 5.8-8.2), with a 2-year OS rate of 57.3%. The CA125 response rate was 81.5%, with a median CA125 reduction of 70.2% (IQR 62.6-93.4), and 48.1% of patients achieved CA125 normalization. Prior chemotherapy lines, bevacizumab/PARP inhibitors exposure, and a shorter platinum-free interval did not alter the therapeutic efficacy (all P > 0.05). Among 12 patients evaluable per RECIST v1.1 criteria, the ORR was 58.3%, the median DOR was 7.0 months (95% CI 4.9-9.0), and the disease control rate was 100%. Grade 3-4 treatment-related adverse events occurred in 10 patients, mostly hematologic toxicities. CONCLUSION: This chemotherapy regimen demonstrated satisfactory therapeutic efficacy and manageable toxicity in heavily pretreated PROC, suggesting its potential as a viable treatment alternative.
Minimizing the risks of stereotactic brain biopsy in suspected central nervous system lymphoma: a retrospective database study.
Li A, Saleh S, Sharba N … +9 more , Guivatchian E, Sagher O, Sullivan SE, Heth JA, Hollon TC, Thompson BG, Pandey AS, Umemura Y, Al-Holou WN
J Cancer Res Clin Oncol · 2026 Mar · PMID 41886097 · Full text
BACKGROUND: Stereotactic brain biopsy is widely used to confirm the diagnosis of central nervous system (CNS) lymphoma; however, few studies have investigated the perioperative factors that impact the procedure’s clinica...
BACKGROUND: Stereotactic brain biopsy is widely used to confirm the diagnosis of central nervous system (CNS) lymphoma; however, few studies have investigated the perioperative factors that impact the procedure’s clinical utility and outcome. METHOD: We retrospectively reviewed all patients at our institution who underwent brain biopsy and were confirmed to have CNS lymphoma diagnosis in years 2001–2021. Clinical history, imaging, intraoperative data, and post-biopsy outcomes were obtained. Associations between perioperative factors and postprocedural morbidity/mortality were analyzed using univariate and multivariate models. RESULTS : CNS lymphomas were diagnosed in 75 patients via 79 separate biopsies, of which 12 (16%) had a prior diagnosis of lymphoma (CNS or systemic). Postoperative 30-day mortality was 8.9%. Intraoperative bleeding was noted in 6 patients (7.6%), postoperative hemorrhage in 4 patients (5.1%). We identified several factors leading to poor outcomes. Biopsy of deep-brain structures (thalamus and basal ganglia) was associated with higher rates of postoperative hemorrhage (17.6% vs. 1.6%, p = 0.030) and discharge to hospice (35.3% vs. 9.7%, p = 0.018). Biopsy at multiple depths, a modifiable risk factor, was associated with worse survival after multivariate analysis (p = 0.036). In patients with a history of systemic diffuse large B-cell lymphoma (DLBCL), all brain biopsies diagnosed DLBCL; several patients with non-DLBCL were diagnosed with other pathologies including glioblastoma. CONCLUSION: Several variables were associated with poor outcomes after biopsy for suspected CNS lymphoma. Our findings support avoiding biopsy of multiple depths unless critical. These factors should be considered and further risk stratification for patient selection is necessary to optimize the clinical utility of brain biopsy.
GALNT1 emerges as a potential therapeutic target in breast cancer.
Li J, Zhong P, Li X … +4 more , Huang R, Zhan Z, Li J, Mao M
J Cancer Res Clin Oncol · 2026 Mar · PMID 41880012 · Full text
PURPOSE: GALNT1, a key enzyme mediating O-GalNAc glycosylation, has not been fully characterized in the tumor microenvironment. This study aimed to investigate its expression pattern, molecular mechanisms, and clinical r...
PURPOSE: GALNT1, a key enzyme mediating O-GalNAc glycosylation, has not been fully characterized in the tumor microenvironment. This study aimed to investigate its expression pattern, molecular mechanisms, and clinical relevance in breast cancer. METHODS: Public datasets (TCGA, GEO, CPTAC) and single-cell transcriptomic data were integrated to analyze GALNT1 expression across cancer types and at the single-cell resolution. The expression and subcellular localization of GALNT1 in breast cancer were verified using qRT-PCR, Western blot, and immunofluorescence staining. Functional assays were conducted to assess its effects on cell proliferation, migration, and O-glycosylation, while CCK-8 assays were used to evaluate sensitivity to bortezomib. RESULTS: GALNT1 was significantly upregulated in primary breast cancer as well as multiple other malignancies. In vitro experiments demonstrated that GALNT1 promoted breast cancer cell proliferation, migration, and O-glycosylation. Immunofluorescence staining revealed widespread GALNT1 expression in tumor epithelial cells and cancer-associated fibroblasts (CAFs), with colocalization to the Tn antigen. Notably, GALNT1-mediated O-glycosylation was associated with resistance to bortezomib. High GALNT1 expression correlated with increased infiltration of CAFs and M2 macrophages, and reduced CD8⁺ T cell infiltration. Single-cell transcriptomic analysis further confirmed CAF-specific enrichment and elevated epithelial-mesenchymal transition (EMT) scores. CONCLUSIONS: GALNT1 is highly expressed in breast cancer, where it promotes tumor progression, bortezomib resistance through O-glycosylation, and immune microenvironment remodeling. The data imply that GALNT1 could represent a novel therapeutic candidate in breast cancer.
Treatment paradigms in undifferentiated pleomorphic sarcoma of bone: lessons learned from osteosarcoma and questions that remain commentary on: Bielack SS et al. J Cancer Res Clin Oncol (2026).
Geçgel A, Peker P
J Cancer Res Clin Oncol · 2026 Mar · PMID 41874771 · Full text
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The association between age and lymph node status among patients with breast cancer after neoadjuvant chemotherapy: Eastern European population-based retrospective cohort study.
Torres K, Bogacz P, Sędłak K … +10 more , Mlak R, Staśkiewicz M, Pelc Z, Kubiak M, Kurylcio A, Nowikiewicz T, Grasso SV, Skórzewska M, Gumbs A, Rawicz-Pruszyński K
J Cancer Res Clin Oncol · 2026 Mar · PMID 41865186 · Full text
BACKGROUND: It is estimated that the incidence of breast cancer (BC) will steadily increase, particularly within the elderly (≥ 65 years of age) group of patients. In this population, both breast-conserving treatment (BC...
BACKGROUND: It is estimated that the incidence of breast cancer (BC) will steadily increase, particularly within the elderly (≥ 65 years of age) group of patients. In this population, both breast-conserving treatment (BCT) and mastectomy have been proven effective in terms of overall survival (OS). However, the debate over the necessity of axillary procedures (sentinel node biopsy, axillary lymph node dissection) among elderly BC individuals remains ongoing. With limited data on clinical outcomes among elderly BC patients receiving neoadjuvant chemotherapy (NAC) in Eastern European individuals, the aim of the current study was to evaluate the association between age and LN status on clinical outcomes and OS in BC patients after NAC. In addition, the influence of demographic and clinical factors on the incidence of LN metastasis was assessed. METHODS: Female patients with histologically confirmed non-metastatic (cT1-4N0-3M0) BC who underwent multimodal treatment and with curative intent between 2013 and 2023 in two Polish university centers were included in the study and divided into elderly (≥ 65) and non-elderly (< 65) groups. Patients who had not undergone NAC or had incomplete histopathological report or survival data were excluded. RESULTS: A total of 637 patients were included in the final analytic cohort. In both the elderly (n = 136) and non-elderly (n = 501) groups, higher clinical tumor (cT) stage, higher post treatment pathological tumor (ypT) stage, and clinically positive nodes (cN+) were associated with increased odds of postoperative metastatic LNs (all p < 0.01). Residual nodal disease (ypN+) and higher ypT stage were associated with worse OS in the non-elderly group, (HR = 5.95; 95% CI 2.38–14.90; p = 0.0002; and HR = 1.99; 95% CI 1.09–3.63; p = 0.0259, respectively). In contrast, in the elderly group, ypN status was not significantly associated with OS. CONCLUSION: In this Eastern European cohort of BC patients treated with NAC, post-treatment lymph node status showed age-dependent prognostic value. Residual nodal disease remained a strong adverse prognostic factor in non-elderly patients, whereas its association with overall survival was not observed in elderly patients. These findings support further research on age-tailored axillary strategies after NAC, ideally in prospective studies.
KLRG1 defines a distinct tumor-infiltrating granzyme K+ CD8 + T cell population.
Thomas J, Kennedy S, Darcy S … +10 more , Malaco H, Chambwe N, Kamdar D, Periera L, Salama A, Scarola D, Miles B, Frank D, Seetharamu N, Mandal R
J Cancer Res Clin Oncol · 2026 Mar · PMID 41857425 · Full text
PURPOSE: Emerging evidence indicates that granzyme K expressing tumor infiltrating CD8 + T-cells play a critical role in mediating anti-tumor T-cell immunity and immunotherapy treatment response. However, precise charact...
PURPOSE: Emerging evidence indicates that granzyme K expressing tumor infiltrating CD8 + T-cells play a critical role in mediating anti-tumor T-cell immunity and immunotherapy treatment response. However, precise characterization and cell surface markers for the viable isolation of these cells from tumor samples are lacking. METHODS: We constructed a tumor-infiltrating CD8 + T cell subpopulation atlas (n = 286,827 cells) by integrating single-cell RNA sequencing datasets from two immunotherapy-treated patient cohorts with aerodigestive tract malignancies. This unified dataset facilitated detailed mapping of transcriptional trajectories and stringent identification of distinctive cell surface markers across major CD8 + tumor-infiltrating lymphocyte (TIL) compartments. RESULTS: Analysis of the CD3 + CD8+ TIL transcriptional landscape revealed three predominant populations across all tumor types and treatment conditions: stem-like cells, dysfunctional effector cells, and GZMK+ effector cells. Notably, the GZMK+ effector population displayed a distinctive transcriptional profile lacking positive enrichment of pre-defined gene sets, suggesting a previously poorly characterized subpopulation without established cell surface markers. We performed high-dimensional flow cytometry on primary human tumor samples to validate candidate CD8 + TIL subpopulations. Through validation in primary human tumors, we established that cell surface KLRG1 reliably identifies and enables viable isolation of the GZMK+ effector TIL population. Concurrently, we demonstrated that dysfunctional and stem-like populations can be effectively isolated as KLRG1-CD39 + and KLRG1-CD39- CD55 + subsets, respectively. Importantly, accurate enrichment occurs despite decreased starting cell type proportion. CONCLUSIONS: Our characterization of CD8 + TIL subpopulations and validation of their distinguishing surface markers establishes a robust platform for isolation and protein-level granzyme assessment of these key cells in patient samples.
Diagnostic and therapeutic challenges in claudin 18.2-positive gastric cancer treated with zolbetuximab: Intrapatient heterogeneity or secondary loss of expression?
Morath O, Lindig U, Katenkamp K … +10 more , Gassler N, Haziri D, Auletta V, Bauerschlag D, Franiel T, Bergener M, Griessbach AS, Ernst T, Hochhaus A, Crodel CC
J Cancer Res Clin Oncol · 2026 Mar · PMID 41854734 · Full text
BACKGROUND: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target in advanced gastric cancer (GC). Data on resistance to zolbetuximab due to secondary antigen loss or baseline intrapatient heterogeneity a...
BACKGROUND: Claudin 18.2 (CLDN18.2) has emerged as a promising therapeutic target in advanced gastric cancer (GC). Data on resistance to zolbetuximab due to secondary antigen loss or baseline intrapatient heterogeneity are sparse. CASE PRESENTATION: A young female patient with advanced GC and severe anemia and thrombocytopenia due to bone marrow carcinomatosis, treated with zolbetuximab-based therapy, exhibited discordant CLDN18.2 expression between primary and metastatic sites. Histological analysis of the resected Krukenberg metastasis revealed CLDN18.2 negativity, contrasting with the strong, diffuse expression in the primary tumor and bone marrow metastases. Subsequent disease progression occurred predominantly in lymph node metastases. DISCUSSION: This case reveals the potential clinical impact of the heterogeneity of CLDN18.2 expression or secondary loss of antigen on the efficacy of CLDN18.2-targeted therapy. Reassessment of biomarkers at progression could be considered to optimize personalized treatment strategies. Furthermore, this case supports the safety of administering zolbetuximab-based therapy in the setting of bone marrow carcinomatosis, even in the presence of severe thrombocytopenia (platelet count < 50 × 109/l). To our knowledge, this represents the first documented case of CLDN18.2-positive gastric cancer identified by bone marrow biopsy worldwide.
No-touch versus conventional radiofrequency ablation for treating solitary recurrent hepatocellular carcinoma ≤ 3 cm: a retrospective cohort study.
Wu G, Ou X, Zou M … +5 more , Xia F, Zhang L, Feng K, Ma K, Wang Q
J Cancer Res Clin Oncol · 2026 Mar · PMID 41848917 · Full text
OBJECTIVE: This study aimed to compare the outcomes of no-touch radiofrequency ablation (NT-RFA) and conventional RFA (C-RFA) in the treatment of solitary recurrent hepatocellular carcinoma (rHCC) ≤ 3 cm. METHODS: 255 pa...
OBJECTIVE: This study aimed to compare the outcomes of no-touch radiofrequency ablation (NT-RFA) and conventional RFA (C-RFA) in the treatment of solitary recurrent hepatocellular carcinoma (rHCC) ≤ 3 cm. METHODS: 255 patients with rHCC treated with RFA in our center from January 2017 to December 2023 were retrospectively analyzed (NT-RFA: 63, C-RFA: 192 patients). Short- and long-term outcomes were compared, and survival rates were calculated. RESULTS: The ablation range and safety margin differed significantly between the two groups (both p < 0.01). The 1-, 3-, and 5- years overall survival (OS) rates were 96.83%, 75.51% and 45.61% respectively in the NT-RFA group, while 97.39%, 77.48% and 48.56% in the C-RFA group, with no significant difference between the two groups (P = 0.510). The 1-, 3-, and 5-year recurrence-free survival (RFS) rates in the NT-RFA group were 73.02%, 46.22% and 36.77%, respectively, while 69.70%, 38.95% and 27.78% in the C-RFA group, with no significant difference between the two groups (P = 0.338). The 1-, 3-, 5-year local tumor progression (LTP) free survival rates in the NT-RFA and C-RFA group were 84.13%, 67.04%, 67.04% and 78.02%, 53.70%, 48.80% respectively, with significant difference between the two groups (P = 0.047). However, there was no significant difference in intrahepatic distant recurrence free survival rates between the two groups (P = 0.068). CONCLUSION: NT-RFA treatment for rHCC ≤ 3 cm is as safe as C-RFA, but it achieves a larger ablation range and safety margin. Although NT-RFA does not significantly improve RFS or OS in rHCC ≤ 3 cm, it significantly reduces the LTP.
Exosome-based vaccines in cancer immunotherapy: antitumor mechanisms, engineering strategies, and challenges.
Zhou H, Shi Y, Wang Y … +1 more , Bai G
J Cancer Res Clin Oncol · 2026 Mar · PMID 41843206 · Full text
Exosome-based vaccines hold significant promise in cancer immunotherapy, yet their native forms face inherent challenges, including imprecise targeting, suboptimal immunogenicity, and poor controllability of antigen load...
Exosome-based vaccines hold significant promise in cancer immunotherapy, yet their native forms face inherent challenges, including imprecise targeting, suboptimal immunogenicity, and poor controllability of antigen loading. This review posits that engineering is pivotal to transforming exosomes from passive carriers into active, programmable therapeutic platforms. We systematically dissect the multifaceted antitumor mechanisms of exosomes and critically evaluate how various engineering strategies (e.g., physical loading, genetic modification, membrane functionalization) are designed to address these specific biological bottlenecks, thereby establishing a coherent "biological limitation-engineering solution" framework. Building on this foundation, we assess their application potential and ongoing challenges in areas such as personalized neoantigen vaccines.
Investigating the oncogenic potential of MTHFD2 in oral squamous cell carcinoma.
Han J, Wang W, Li S … +1 more , Wang J
J Cancer Res Clin Oncol · 2026 Mar · PMID 41831033 · Full text
PURPOSE: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial bifunctional enzyme, is reportedly upregulated in several malignancies, demonstrating cancer-associated dysregulation. However, its functional...
PURPOSE: Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial bifunctional enzyme, is reportedly upregulated in several malignancies, demonstrating cancer-associated dysregulation. However, its functional contribution to oral squamous cell carcinoma (OSCC) progression remains unexplored. Therefore, this study aimed to investigate the role of MTHFD2 in OSCC development. METHODS: MTHFD2 expression was assessed in OSCC biospecimens using integrated bioinformatics, immunohistochemistry, and immunoblotting techniques. Survival analysis was conducted utilizing the Kaplan–Meier methodology. The MTHFD2-associated mechanisms involved in OSCC were explored via enrichment analysis. Genetic suppression of MTHFD2 was employed to evaluate the functional consequences on OSCC cell proliferation (Cell Counting Kit-8 assay), apoptosis (flow cytometry), migration (wound healing assay), and invasion (Matrigel transmigration). RESULTS: MTHFD2 expression was considerably elevated in OSCC lesions and cellular models. MTHFD2 overexpression in OSCC tissues correlated with advanced Tumor, Node, and Metastasis stage (P = 0.002), regional lymph node metastasis (P = 0.043), and elevated Ki67 expression (P < 0.001). Furthermore, increased MTHFD2 levels were associated with poor overall survival outcomes in patients with OSCC (P < 0.05). Pathway enrichment analysis revealed that MTHFD2 upregulation was closely linked to the dysregulation of key neoplastic processes. Stable MTHFD2 depletion attenuated cell proliferation in vitro and diminished xenograft tumorigenicity in vivo (P < 0.05). Additionally, MTHFD2 ablation induced OSCC cell apoptosis and reduced cell migration and invasion. CONCLUSION: This study indicates that MTHFD2 is critical for OSCC progression and may serve as a potential therapeutic target, though further validation is needed to confirm its independent prognostic value and clinical applicability.
The features and prognostic value of ARID1A mutation and protein expression in endometrial cancer of no specific molecular profile (NSMP) subtype: a retrospective study in a large Chinese cohort.
Yuan X, Cai M, Yu C … +4 more , Zhai Z, Zhou X, Wang H, Ren Y
J Cancer Res Clin Oncol · 2026 Mar · PMID 41826754 · Full text
PURPOSE: Endometrial cancer (EC) of no specific molecular profile (NSMP) subtype constitutes the majority of EC and shows significant heterogeneity. This study aims to explore the role of ARID1A mutation and protein expr...
PURPOSE: Endometrial cancer (EC) of no specific molecular profile (NSMP) subtype constitutes the majority of EC and shows significant heterogeneity. This study aims to explore the role of ARID1A mutation and protein expression in NSMP EC patients in a large Chinese cohort. METHODS: A retrospective analysis was conducted on patients with NSMP EC who underwent primary surgery and next-generation sequencing (NGS). Clinicopathologic features, ARID1A mutation, protein expression and progression-free survival (PFS) were analysed in our study. RESULTS: A total of 547 patients were enrolled in the study, and 151 patients with NSMP were included in the final analyses. ARID1A mutations were identified in 49.0% (74/151) patients, in which 85.1% (63/74) of them were loss-of-function mutations and 27.0% (20/74) with multiple mutations. Compared to patients with ARID1A wild-type, those with ARID1A mutations were older (p = 0.032) and had higher staging (p = 0.022), and ARID1A mutation was associated with poorer PFS (p = 0.019). Among 90 patients with immunohistochemistry (IHC), the absence of ARID1A protein expression was significantly associated with ARID1A mutation (p < 0.001), especially with ARID1A multiple mutations (p = 0.042). The aberrant PI3K pathway was more likely to occur in patients with ARID1A mutations (p = 0.006). ER/PR negative expression, PIK3CA hotspot mutations, with ARID1A mutations were correlated with poor PFS (p < 0.001; p = 0.013). CONCLUSION: ARID1A mutation was associated with worse PFS for patients with NSMP. ARID1A protein expression was significantly associated with ARID1A mutation. ARID1A mutation, with ER/PR expression and PIK3CA mutation status, could serve as the potential biomarkers to subclassify NSMP subtype and provide more precise therapeutic target.
Efficacy and safety of neoadjuvant chemoimmunotherapy versus neoadjuvant chemoradiotherapy in locally advanced resectable esophageal squamous cell carcinoma.
Jiang Y, Wu Z, Wang W … +2 more , Yu J, Gao A
J Cancer Res Clin Oncol · 2026 Mar · PMID 41820752 · Full text
OBJECTIVE: To compare the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) versus chemoimmunotherapy (NCIT) in resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: Patients with L...
OBJECTIVE: To compare the efficacy and safety of neoadjuvant chemoradiotherapy (NCRT) versus chemoimmunotherapy (NCIT) in resectable locally advanced esophageal squamous cell carcinoma (LA-ESCC). METHODS: Patients with LA-ESCC who underwent NCIT or NCRT were retrospectively enrolled between November 2017 and April 2024. Propensity score matching (PSM) was applied to balance the baseline characteristics. Treatment response, survival outcomes, and safety were compared between groups. RESULTS: 501 patients were enrolled, with 204 in the NCRT group and 297 in the NCIT group. After PSM, 148 matched pairs were analyzed. The NCRT group had a superior objective response rate (ORR) (68.2% vs. 54.7%, P = 0.023), pathological complete response (pCR) rate (46.6% vs. 20.9%, P < 0.001), tumor regression grade (TRG) distribution (P < 0.001), 2-year disease-free survival (DFS) (77.4% vs. 66.0%, P = 0.007) and overall survival (OS) rates (93.7% vs. 81.5%, P < 0.001) compared with NCIT group. The survival benefit was confined to patients who did not achieve pCR (both P < 0.05). Deeper tumor regression was strongly associated with improved DFS and OS (P for trend < 0.001). The incidence of postoperative complications and adverse events was comparable between groups. However, grade ≥ 3 hematologic toxicity was significantly higher with NCRT (36.5% vs. 6.8%, P < 0.001). CONCLUSION: NCRT demonstrated superior pCR rates and mid-term survival outcomes to NCIT in resectable LA-ESCC, likely related to deeper tumor regression. TRG scores after neoadjuvant therapy predict graded survival benefit, provide more refined prognostic stratification, and complement pCR. Although postoperative complication rates were comparable, NCRT induced higher grade ≥ 3 hematologic toxicity, necessitating vigilant monitoring.
Ubiquitin C-terminal hydrolase L3 promotes liver cancer cell proliferation by modulating the AMP-activated protein kinase signaling pathway.
Liu Y, Lu J, Wang H … +6 more , Sun S, Guo B, Wang X, Wang B, Li Y, Wu T
J Cancer Res Clin Oncol · 2026 Mar · PMID 41820631 · Full text
PURPOSE: The deubiquitinase Ubiquitin C-Terminal Hydrolase L3 (UCHL3) is highly expressed in multiple cancer types and generally considered as an oncogene. However, its functions in liver cancer are unclear. This study i...
PURPOSE: The deubiquitinase Ubiquitin C-Terminal Hydrolase L3 (UCHL3) is highly expressed in multiple cancer types and generally considered as an oncogene. However, its functions in liver cancer are unclear. This study investigated the role of UCHL3 in liver cancer cell growth and evaluated its potential clinical significance as a prognostic marker. METHODS: The expression of UCHL3 in cancer and its correlations with clinical parameters were assessed by using TCGA databases. Gene expression was analyzed by real time-PCR, Western Blotting, and immunostaining. Colony formation assays were performed and growth curve were measured to evaluate the function of UCHL3 in liver cancer cell proliferation. Gene Set Enrichment Analysis (GSEA) was used to explore enriched pathways. RESULTS: We found that UCHL3 was essential in promoting liver cancer cell proliferation. It was highly expressed in liver cancer tissues and was a negative prognostic marker for liver cancer. Knocking down UCHL3 reduced the expression of cell cycle regulators, such as Cyclin A2, Cyclin B1 and MAD2, inhibiting cell cycle progression. The inhibition was partially due to the alteration of autophagy upon UCHL3 deprivation, as disruption of autophagy restored the protein level of Cyclin B1 and reversed cell cycle arrest. Suppressing UCHL3 was associated with the activation of AMP-activated protein kinase (AMPK) signaling pathway, which was important in controlling autophagy activation. CONCLUSION: UCHL3 may negatively modulate the AMPK pathway and autophagy in liver cancer to maintain the expression of cell cycle regulators and facilitate cell proliferation. Targeting overexpressed UCHL3 may be feasible to inhibit liver cancer progression.
Prognostic factors for lymph node infestation, long-term survival and recurrence rates in patients with vaginal cancer: a population-based study in Germany.
Wenning S, Gerken M, Papathemelis T … +15 more , Ortmann O, Franke B, Wittenberg I, Walter C, Schneider C, Sackmann A, Zeissig SR, Reinwald F, Rath N, Weitmann K, Müller-Nordhorn J, Herr C, Klinkhammer-Schalke M, Marnitz S, Sturm-Inwald EC
J Cancer Res Clin Oncol · 2026 Mar · PMID 41814047 · Full text
PURPOSE: Vaginal cancer (ICD-10: C52) is one of the rarest gynecological malignancies, with limited research on its frequency, long-term survival, therapy-dependent survival, and follow-up of recurrences. This knowledge...
PURPOSE: Vaginal cancer (ICD-10: C52) is one of the rarest gynecological malignancies, with limited research on its frequency, long-term survival, therapy-dependent survival, and follow-up of recurrences. This knowledge deficit may lead to potential consequences such as medical over-, under- or wrong therapy. METHODS: This nationwide retrospective population-based registry study analyzed patients with vaginal cancer diagnosed between 2000 and 2022 in Germany. A total cohort of 1325 patients was included. To assess prognostic factors related to lymph node involvement, overall survival, recurrence rates, and therapy-dependent survival were analyzed using binary logistic regression, the Kaplan-Meier method, and univariable and multivariable Cox regression. RESULTS: Mean age at diagnosis was 68.5 years and median age was 70.4 years. 30.0% (n = 398) of patients showed lymph node involvement. Younger age at diagnosis (< 60 years), larger tumor size, and lymphatic invasion were noted as significant risk factors for lymph node involvement in multivariable analysis. The 5-year overall survival rate was 53.8% (95%-CI 50.9–56.7), significantly influenced by age at diagnosis, nodal status, and tumor size in multivariable analysis. Cumulative recurrence rates for locoregional and distant metastases were 20.4% and 14.3% after 5 years, increasing to 24.3% and 16.5% after 10 years. The most common primary treatment was surgery (39.2%, n = 454). Surgery plus radiochemotherapy (OP + RCT) provided the most favorable outcome as a primary treatment, whereas radiotherapy alone showed the least benefit of all treatment options. CONCLUSION: Our study identifies important prognostic factors influencing vaginal cancer survival and offers information on treatment optimization.
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