Journal Of Cancer Research And Clinical Oncology[JOURNAL]
Sun
200 papers
The relevance of mA RNA modifications in cancer stem cells.
Monteiro A, Pádua D, Gonçalves C … +2 more , Mesquita P, Almeida R
J Cancer Res Clin Oncol · 2026 Jun · PMID 42262586 · Publisher ↗
Cancer is a multifactorial disease, driven by dysregulation of cellular processes that are controlled by the complex influence of DNA and RNA-level regulatory mechanisms. Epitranscriptomics has surfaced as a prominent fi...
Cancer is a multifactorial disease, driven by dysregulation of cellular processes that are controlled by the complex influence of DNA and RNA-level regulatory mechanisms. Epitranscriptomics has surfaced as a prominent field in cancer research, providing a clearer understanding of post-transcriptional regulation of gene expression. In particular, N-methyladenosine (mA) is the most abundant internal modification in eukaryotic mRNA, and has emerged as a key regulator of post-transcriptional gene expression. Through the coordinated activity of methyltransferases ("writers"), demethylases ("erasers") and binding proteins ("readers"), mA dynamically modulates important RNA processing steps, including translation, stability, decay and splicing. Notably, mA regulatory proteins are implicated in several stemness pathways acting as oncogenic drivers or tumor suppressors in a highly context-dependent manner. This regulatory flexibility is particularly relevant in cancer stem cells (CSCs), a highly plastic subpopulation involved in tumor initiation, progression, metastasis and therapy resistance. Indeed, some of the major challenges in oncology arise from cancer cell adaptability, tumor heterogeneity and microenvironment-dependent outcomes, processes in which mA emerges as a critical regulatory layer. This review summarizes the mechanisms of mA regulation and its biological effects, and provides an overview of the influence of mA in CSC phenotypes. Finally, it explores how mA affects therapeutic responses, future perspectives in oncology and the key challenges currently under investigation in this field.
Prognostic influence of small leucine-rich proteoglycans on serous ovarian cancer.
Surmann H, Bartha A, Győrffy B … +3 more , Kiesel L, Hanker L, Götte M
J Cancer Res Clin Oncol · 2026 Jun · PMID 42251619 · Full text
PURPOSE: Ovarian cancer is one of the most lethal cancers in women worldwide. To be able to offer successful treatment and improve the prognosis, knowledge of factors influencing the tumor microenvironment is indispensab...
PURPOSE: Ovarian cancer is one of the most lethal cancers in women worldwide. To be able to offer successful treatment and improve the prognosis, knowledge of factors influencing the tumor microenvironment is indispensable. In this context, the influence of the extracellular matrix on tumor progression is increasingly recognized. Of note, preclinical data in cell line and animal models have suggested that several members of the small leucine-rich proteoglycan (SLRP) family are mechanistically involved in the regulation of tumor progression. We hypothesized that dysregulation of SLRP expression may have a prognostic value in ovarian cancer. METHODS: To distinguish whether this expression is altered in the cells themselves or in the extracellular matrix, quantitative Real-Time PCR was performed on ovarian cancer cell lines and complemented by analysis of CCLE datasets. We used Kaplan-Meier survival curves to investigate whether a high or low mRNA expression influences the survival of ovarian cancer patients. Finally, the interactions of the SLRPs were investigated using a STRING analysis. RESULTS: We demonstrated the potential beneficial effect of a low mRNA expression of most SLRPs on the prognosis of serous ovarian cancer. STRING analysis revealed interactions with other proteins already known to influence tumor behavior and metastasis of various carcinomas. CONCLUSION: These findings suggest that SLRPs may be involved in ovarian cancer biology and could represent candidates for further mechanistic investigation. However, their potential relevance for therapeutic strategies, including treatment response, requires additional functional validation.
De-escalating axillary surgery in early breast cancer: external validation of a retrospective cohort.
Landry M, Favier A, Ksantini F … +3 more , Gabro A, Canlorbe G, Uzan C
J Cancer Res Clin Oncol · 2026 Jun · PMID 42240899 · Publisher ↗
BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard for axillary staging in early breast cancer, yet its relevance is increasingly questioned in patients with favorable tumor biology when nodal status does not...
BACKGROUND: Sentinel lymph node biopsy (SLNB) is the standard for axillary staging in early breast cancer, yet its relevance is increasingly questioned in patients with favorable tumor biology when nodal status does not influence systemic treatment decisions. METHODS: We conducted a retrospective, single-center observational study including 162 women with clinically and sonographically node-negative (cN0) pT1 invasive breast cancer treated between 2019 and 2024 at a French university hospital. All patients underwent axillary staging and had complete molecular profiling. Among the 25 patients with pathologically positive nodes (pN+), two multidisciplinary team (MDT) discussions were simulated: one blinded to nodal status (limited-information MDT) and one with complete clinicopathologic data (full-information MDT). Recommendations for adjuvant chemotherapy and genomic testing (Oncotype DX) were compared. RESULTS: Most tumors were hormone receptor-positive (90%) and HER2-negative (87%); 9% were triple-negative. Despite negative preoperative axillary ultrasound, nodal involvement was identified in 25 patients (15%). In the limited-information MDT, chemotherapy was recommended in 8 patients and genomic testing in 11 patients. In contrast, the full-information MDT recommended chemotherapy in 16 patients and genomic testing in 9 patients, with 2 additional patients ultimately receiving chemotherapy. Omission of nodal status during MDT deliberation was associated with a significant reduction in chemotherapy recommendations (p < 0.01). Genomic testing contributed to treatment de-escalation in both scenarios. CONCLUSIONS: In selected patients with pT1 breast cancer, omission of axillary nodal status during MDT decision-making may safely reduce adjuvant chemotherapy use without compromising treatment planning, supporting current axillary de-escalation strategies.
Diagnostic performance of the NI-RADS system for detecting recurrence in head and neck squamous cell carcinoma: a monocentric pilot study.
Greco S, Villanova I, Maggialetti N … +7 more , Lorusso G, Lucarelli NM, Morelli C, Dipalma C, Brunese MC, Copelli C, Ianora AAS
J Cancer Res Clin Oncol · 2026 Jun · PMID 42240675 · Publisher ↗
BACKGROUND: This pilot study evaluates the diagnostic performance and clinical relevance of the Neck Imaging Reporting and Data System (NI-RADS) in the post-treatment surveillance of patients with head and neck squamous...
BACKGROUND: This pilot study evaluates the diagnostic performance and clinical relevance of the Neck Imaging Reporting and Data System (NI-RADS) in the post-treatment surveillance of patients with head and neck squamous cell carcinoma (HNSCC), using computed tomography (CT) and magnetic resonance imaging (MRI). METHODS: This retrospective study included 25 patients with histologically confirmed HNSCC treated between August 2021 and December 2024. All patients underwent at least two post-treatment CT or MRI scans, independently reviewed by two radiologists and classified according to the NI-RADS system. Recurrence was confirmed by histopathology or clinical and imaging follow-up. Diagnostic performance metrics, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, were calculated using a threshold of NI-RADS ≥ 3. Receiver operating characteristic (ROC) analysis was performed for primary and neck sites. RESULTS: A total of 56 imaging studies and 112 anatomical sites were assessed. Recurrence was confirmed in 36% of primary sites and 27% of neck sites. NI-RADS category 1 showed 0% recurrence, whereas category 4 showed 100% recurrence for both anatomical sites. For the primary site, sensitivity was 80% (95% CI: 56-94%) and specificity 92% (95% CI: 78-98%), with an accuracy of 88% (95% CI: 76-95%). For neck sites, sensitivity was 80% (95% CI: 52-96%) and specificity 98% (95% CI: 87-100%), with an accuracy of 93% (95% CI: 82-98%). The area under the ROC curve was 0.86 for the primary site and 0.88 for the neck site. CONCLUSIONS: NI-RADS showed good diagnostic performance for detecting locoregional recurrence in post-treatment surveillance of HNSCC using CT and MRI. However, given the retrospective design and limited sample size, these findings should be considered preliminary and require confirmation in larger prospective studies.
Investigation of a GPC1-targeted and LIFU-responsive nanoplatform with ADV effect for visualized chemo-sonodynamic therapy against pancreatic ductal adenocarcinoma.
Ren B, Quan G, Li H … +6 more , Ye L, Xie X, Yu J, Xu J, Li J, Wong C
J Cancer Res Clin Oncol · 2026 Jun · PMID 42228190 · Publisher ↗
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Regardless of surgical resection, chemotherapy acts as the first-line treatment for PDAC. However, the clinical outcomes ar...
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Regardless of surgical resection, chemotherapy acts as the first-line treatment for PDAC. However, the clinical outcomes are severely compromised by insufficient tumour-specific targeting, chemoresistance, and systemic toxicity. Thus, new synergistic therapeutic strategies are urgently needed to improve therapeutic efficacy of PDAC. PURPOSE: This study developed a glypican-1 (GPC1)-targeted and low-intensity focused ultrasound (LIFU)-responsive nanoplatform for visualized treatment against PDAC. METHODS: This nanoplatform, termed GCPIP, integrated glypican-1-antibody (GPC1-Ab)-guided tumour-specific targeting, perfluoropentane (PFP)-driven acoustic imaging, ultrasound targeted nanobubble destruction (UTND)-triggered drug release, paclitaxel (PTX)-mediated chemotherapy and sonosensitizer-assisted sonodynamic therapy (SDT). RESULTS: GCPIP exhibited favourable physicochemical properties as a delivery system, showing excellent stability, responsive drug release behaviour, and robust ROS-generating capacity. In vitro studies revealed that GCPIP exhibited outstading tumour-targeting capability and potent inhibitory activity against PDAC tumour cells. Near-infrared fluorescence (NIRF) imaging in vivo demonstrated that GCPIP displayed a biodistribution profile broadly consistent with typical metabolic fate of nanoparticles, enabling preferential intratumoural accumulation. Leveraging acoustic droplet vaporization (ADV) effect of PFP, ultrasound (US) imaging further allowed real-time visualization of the uptake and spatial distribution of GCPIP within the tumour. Importantly, GCPIP elicited a pronounced synergistic antitumour effect upon LIFU, as evidenced by substantial inhibition in both tumour volume and tumour weight. Additionally, GCPIP exhibited favourable biosafety in vivo. CONCLUSION: GCPIP successfully achieved US imaging, tumour-specific drug delivery, spatiotemporally controlled drug release, and amplified chemo-sonodynamic therapy, providing a promising strategy to overcome chemoresistance of PDAC and reduce systemic toxicity.
Investigation of a methylated BCAT1 and IKZF1 circulating tumour DNA blood test for monitoring treatment response in patients with colorectal cancer.
Rafeeu R, Symonds EL, Michael MZ … +5 more , Cornthwaite K, Pedersen SK, Smith RJ, Young GP, Winter JM
J Cancer Res Clin Oncol · 2026 Jun · PMID 42228147 · Publisher ↗
PURPOSE: Colorectal cancer (CRC) treatment failure results in high mortality. The current CRC treatment response monitoring blood biomarker carcinoembryonic antigen (CEA) lacks specificity. Methylated BCAT1/IKZF1 circula...
PURPOSE: Colorectal cancer (CRC) treatment failure results in high mortality. The current CRC treatment response monitoring blood biomarker carcinoembryonic antigen (CEA) lacks specificity. Methylated BCAT1/IKZF1 circulating tumour DNA (ctDNA) indicates CRC, but its utility during therapy is uncertain. This study examined whether during-treatment measurement of BCAT1/IKZF1 ctDNA reflects CRC treatment efficacy. METHODS: Plasma was collected from CRC patients before and during chemotherapy, targeted therapy and/or radiotherapy. Cell-free DNA was extracted, bisulphite-converted and assayed via multiplex qPCR for BCAT1/IKZF1 methylation (%pg/ACTB). Patients with detectable ctDNA pre-treatment were included. CEA was measured via chemiluminescent immunoassay. Radiological treatment response assessments were performed ± 3 months of blood collection or < 8 months post-treatment. Biomarker levels were compared using Mann-Whitney U and Kruskal-Wallis tests. RESULTS: 56 samples from 29 patients (64.3% male, median age 55 years) were analysed. Patients with residual cancer had higher ctDNA levels (median 0.036%, IQR 0-1.17%) than cancer-free patients (0%, IQR 0-0.005%; p < 0.05). There were no significant differences for CEA. When normalised to pre-treatment measurements, treatment-responders demonstrated a median 100% ctDNA reduction from baseline (IQR - 100% to - 7.53%), which was greater than non-responders (0.13% reduction, IQR - 38.1% to + 0.03%; p < 0.001). Responders also demonstrated greater CEA reduction (median - 1.50 ng/mL, IQR - 6.28 to 0.18 ng/mL) compared to non-responders (median 2.3 ng/mL, IQR - 0.50 to 17.7 ng/mL; p = 0.001). CONCLUSIONS: Methylated BCAT1/IKZF1 ctDNA reflects treatment response, offering a tool for personalised treatment.
Predictive value of Slug-positive circulating tumor cells for neoadjuvant chemotherapy response in mesenchymal malignancies.
He N, Liu S, Cui H … +7 more , Feng J, Liang W, Yao B, Amu F, Xu B, Fan Q, Hao P
J Cancer Res Clin Oncol · 2026 May · PMID 42223483 · Publisher ↗
PURPOSE: To evaluate the predictive value of Slug-positive circulating tumor cells (CTCs) for responses to neoadjuvant chemotherapy in mesenchymal malignancies. METHODS: Prospective observational analysis of 59 patients...
PURPOSE: To evaluate the predictive value of Slug-positive circulating tumor cells (CTCs) for responses to neoadjuvant chemotherapy in mesenchymal malignancies. METHODS: Prospective observational analysis of 59 patients receiving neoadjuvant chemotherapy. Peripheral blood was collected pre-treatment for CTC classification. Chemotherapy response was defined as complete response or partial response. Logistic regression identified factors associated with poor response. A combined model integrating Slug epithelial CTCs (ECTCs) and Slug mesenchymal CTCs (MCTCs) was developed. Receiver operating characteristic (ROC) analysis assessed predictive performance; Cox regression evaluated long-term outcomes. RESULTS: Responders had lower Slug MCTCs (2.12 ± 1.84 vs. 3.85 ± 2.25) and higher Slug ECTCs. The combined model showed superior predictive ability (AUC = 0.873) versus single CTC subtypes. Patients with predicted probability > 0.62 were responders. Cox analysis indicated the model predicted long-term prognosis when Slug MCTCs and Slug ECTCs were not simultaneously zero. CONCLUSIONS: Phenotypic heterogeneity influences neoadjuvant chemotherapy response. High Slug MCTCs and low Slug ECTCs indicate insensitivity. The combined model showed promising performance for identifying treatment response and potential prognostic relevance in this prospective cohort.
Photon counting computed tomography in head and neck squamous cell carcinoma: iodine concentration and histopathological features.
Surov A, Diallo-Danebrock R, Sonnemann H … +5 more , Roggel R, Scheer M, Volkenstein S, Wienke A, Borggrefe J
J Cancer Res Clin Oncol · 2026 Jun · PMID 42219395 · Full text
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with increasing relevance in oncologic imaging. Photon-counting computed tomography (PCCT) allows for quantitative assessment in iodine concen...
PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a common malignancy with increasing relevance in oncologic imaging. Photon-counting computed tomography (PCCT) allows for quantitative assessment in iodine concentration (IC) offering new insights into tumor biology. This study aimed to investigate the association between normalized IC (NIC) and histopathological features in HNSCC. METHODS: Eighty-four patients with primary untreated HNSCC underwent contrast-enhanced PCCT of the neck in venous phase. Iodine maps were generated to quantify intratumoral IC. NIC was calculated as the ratio of tumoral IC to aortal IC. Histopathological analysis included tumor stage, tumor grade, Ki 67 proliferation index, tumor cell count and human papillomavirus (HPV) status. Group comparison were conducted using Mann-Whitney-U tests. Interreader agreement was assessed via intraclass correlation coefficient (ICC). Receiver operating characteristic (ROC) analysis was performed to evaluate diagnostic performance of NIC for HPV status. RESULTS: NIC values demonstrated excellent interreader reliability (ICC = 0.96, 95%CI = (0.92; 0.98), p < 0.01). NIC showed an inverse correlation with tumoral cell count (r = -0.24, p = 0.03). Tumors with lymphonodal metastases exhibited lower NIC values compared to N0 tumors (0.42 ± 0.20 vs. 0.54 ± 0.26, p = 0.02). Cell-rich tumors had lower NIC values than cell-poor tumors (0.42 ± 0.18 vs. 0.53 ± 0.26, p = 0.003). HPV negative tumors showed higher NIC values than HPV-positive tumors (0.51 ± 0.23 vs. 0.33 ± 0.18, respectively, p < 0.01). A NIC threshold of ≥ 0.5 predicted HPV negative tumors, demonstrating 54.5% sensitivity and 94.4% specificity, with an AUC of 0.74 (95% CI = 0.62-0.86, p < 0.01). CONCLUSIONS: NIC derived from PCCT is a robust and reproducible imaging parameter in HSNCC. It is moderately associated with tumor cellularity, nodal involvement, and HPV status. Thus, NIC may serve as a valuable adjunct in non-invasive tumor characterization.
Lactylation-augmented DCBLD1-mediated PDIA3 stabilization reprograms glycolysis metabolism in oesophageal cancer.
Yin M, Wang S, Liu H … +3 more , Xu C, Li Q, Sun Y
J Cancer Res Clin Oncol · 2026 May · PMID 42218727 · Publisher ↗
OBJECTIVE: Histone lactylation (Hla) represents a novel epigenetic mark priming cells toward the malignant state. Discoidin, CUB, and LCCL domain-containing type I (DCBLD1) has been reported as a carcinogenic gene so far...
OBJECTIVE: Histone lactylation (Hla) represents a novel epigenetic mark priming cells toward the malignant state. Discoidin, CUB, and LCCL domain-containing type I (DCBLD1) has been reported as a carcinogenic gene so far. This project was focused on the functional role of DCBLD1 in oesophageal cancer through the lactate modification pathway. METHODS: Biological information evaluated DCBLD1, protein disulfide isomerase family A member 3 (PDIA3) expression and the relationship between the two in oesophageal cancer. RT-qPCR and Western blotting were used to detect DCBLD1 and PDIA3 expression. Western blotting also quantified DCBLD1-lysine lactylation (kla) levels. DCBLD1 half-life was checked by chlorhexidine (CHX) assay. EDU, wound healing, transwell, flow cytometry and Seahorse assays individually appraised cell proliferation, migration, apoptosis and glycolysis. Co-IP assay identified DCBLD1-PDIA3 interaction. Xenografted tumorigenesis was estimated, prior to histological assessment by H&E staining. Glucose consumption and lactate production were also examined to detect glycolysis. RESULTS: DCBLD1 was highly expressed in esophageal cancer specimens and cells. DCBLD1 half-life was respectively shortened or prolonged in tumor cells challenged with lactate (LA) or the aerobic glycolysis inhibitor 2-deoxy-d-glucose (2-DG). DCBLD1-Kla levels were up-regulated in oesophageal cancer tissues. Lactate dehydrogenase A (LDHA) interference decreased both DCBLD1 expression and DCBLD1-Kla expression. PDIA3 was highly expressed in oesophageal cancer. DCBLD1 was positively correlated with, and interacted with PDIA3 upon LA stimulation. DCBLD1 knockdown inhibited cell proliferation, migration, glycolysis and induced apoptosis, repressed tumor progress and glycolysis in vivo, which were all partially recovered by PDIA3 overexpression. Further LDHA down-regulation aggravated the impacts of DCBLD1 knockdown and PDIA3 overexpression both in vitro and in vivo. CONCLUSION: It was established that DCBLD1 lactylation bound to PDIA3, contributing to oesophageal cancer malignancy and glycolysis.
Residential radon exposure and lung cancer histology and stage: a population-based ecological study in Central Germany.
Ernst P, Rachow T, Henn S … +6 more , Hammersen JF, Dittrich S, Heßmer A, Hillig A, Heßmer A, Hochhaus A
J Cancer Res Clin Oncol · 2026 May · PMID 42218725 · Full text
PURPOSE: Residential radon exposure is recognised as one of the leading environmental risk factors for lung cancer and acts synergistically with tobacco smoking. Thuringia, Germany, exhibits high geogenic radon potential...
PURPOSE: Residential radon exposure is recognised as one of the leading environmental risk factors for lung cancer and acts synergistically with tobacco smoking. Thuringia, Germany, exhibits high geogenic radon potential; however, population-level associations with lung cancer histology and stage at diagnosis remain insufficiently characterised. METHODS: We conducted a retrospective ecological analysis of 893 lung cancer cases (2018-2022) from the Thuringian State Cancer Registry. Cases from 96 communities were classified as high- or low-radon exposure based on geogenic radon potential and soil radon activity. Demographics, histology and stage were compared between groups. RESULTS: Population-level lung cancer incidence did not differ significantly between low- and high-radon communities, consistent with age- and sex-adjusted Poisson regression showing no association with residential radon exposure (adjusted IRR 1.05, p = 0.473). However, all cases in women younger than 50 years occurred in high-radon communities. Adenocarcinoma was nominally more frequent (56% vs. 48%, p = 0.04), and among patients with small cell lung cancer (SCLC), extensive-stage disease was more common (64% vs. 49%, p = 0.04), with combined SCLC occurring exclusively; however, these findings were not significant after correction for multiple testing. CONCLUSION: In this ecological analysis, residential radon exposure was not associated with annual lung cancer incidence but was linked to tumour histology and stage at diagnosis. Given the ecological design and lack of smoking and occupational exposure data, these findings are hypothesis-generating and warrant further investigation to clarify radon's role in lung cancer biology and prevention.
Diagnostic performance and clinical limitations of sentinel lymph node biopsy in head and neck melanoma: a 20-year retrospective cohort study.
Lükewille L, Wiegand S, Fazel A … +4 more , Kähler KC, Radecker G, Hoffmann M, within the HANSEATIC Head and Neck Oncology Collaboration
J Cancer Res Clin Oncol · 2026 May · PMID 42217063 · Full text
PURPOSE: Sentinel lymph node biopsy (SLNB) is a standard procedure for nodal staging in cutaneous melanoma. However, its diagnostic performance in the head and neck region remains limited due to complex lymphatic drainag...
PURPOSE: Sentinel lymph node biopsy (SLNB) is a standard procedure for nodal staging in cutaneous melanoma. However, its diagnostic performance in the head and neck region remains limited due to complex lymphatic drainage patterns. This study aimed to evaluate the long-term diagnostic accuracy of SLNB in head and neck melanoma and to analyze anatomical and clinical factors associated with false-negative results. METHODS: This retrospective single-center cohort study included patients with cutaneous head and neck melanoma who underwent SLNB between 2002 and 2022. Patients were stratified into two cohorts (2002-2011 and 2012-2022). Detection rates, sensitivity, negative predictive value, and false-negative rates were calculated. Overall survival was analyzed using Kaplan-Meier estimates and compared by log-rank testing. RESULTS: A total of 189 patients were included. Sentinel lymph node detection significantly improved from 78.2% in the earlier cohort to 98.0% in the later cohort (p < 0.0001). Across the combined cohort, SLNB sensitivity was 72.5%, with a false-negative rate of 27.5%. False-negative events predominantly occurred in anatomically complex drainage regions. Sentinel lymph node status was not significantly associated with overall survival (p = 0.627). CONCLUSIONS: Despite substantial improvements in detection rates, SLNB in head and neck melanoma demonstrates clinically relevant limitations in diagnostic sensitivity. The observed false-negative rate highlights a risk of understaging, which may affect eligibility for adjuvant systemic therapies. SLNB findings should therefore be interpreted in the context of anatomical risk patterns and integrated into individualized follow-up strategies. The lack of an association between sentinel lymph node status and overall survival may reflect the impact of modern adjuvant systemic therapies and the distinct biological behavior of head and neck melanoma. However, this finding should be interpreted with caution given the limited sample size. These findings underscore the importance of procedural expertise and risk-adapted surveillance in this anatomically complex region.
Diving into the transcriptional landscape of leukemic stem cells in acute myeloid leukemia at single-cell resolution.
Rzetelska Z, Gil L, Buccisano F … +1 more , Dytfeld D
J Cancer Res Clin Oncol · 2026 May · PMID 42213171 · Publisher ↗
PURPOSE: The aim of this review is to summarize transcriptomic studies using single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq to investigate leukemic stem cells (LSCs) population in acute myeloid leukemia (AML). M...
PURPOSE: The aim of this review is to summarize transcriptomic studies using single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq to investigate leukemic stem cells (LSCs) population in acute myeloid leukemia (AML). METHODS: Literature for inclusion was identified through a PubMed search. Twenty-seven studies were analyzed, covering various aspects of LSCs biology, including epigenetic, transcriptional, and translational gene regulation, metabolic reprogramming or cellular differentiation. RESULTS: The reviewed studies highlight the complexity of LSCs, including their quiescent state, state-to-state cellular plasticity, and metabolic reprogramming from glycolysis to lipogenesis. Comparative analyses of matched diagnostic and post-treatment samples provide insights into the dynamic behavior of LSCs during therapy. The findings also identify potential therapeutic targets and strategies to selectively eradicate LSCs. CONCLUSION: Single-cell RNA sequencing technologies offer unprecedented resolution for studying LSCs in AML, revealing cellular heterogeneity and dynamic evolution within these critical populations. Despite these advances, standardized criteria for LSCs identification are still needed, and longitudinal studies at clinically relevant time points are essential to fully understand their role in disease progression and therapy resistance. Such approaches may ultimately uncover novel therapeutic vulnerabilities and improve clinical management of AML.
Prediction of personalized therapeutic response in pediatric clivus chordoma: chemoresistance test.
Cavalheiro S, Pavon LF, de Farias CB … +14 more , Nascimento FB, Lichtenfels M, Rodrigues JB, Dassi N, Cappellano A, Dastoli PA, de Souza Melo TC, Suzuki F, Watanabe RA, Kim IHT, Tesser-Gamba F, Mendes TB, Onish F, da Costa MDS
J Cancer Res Clin Oncol · 2026 May · PMID 42191910 · Publisher ↗
Precision medicine has expanded therapeutic options for rare central nervous system tumors, yet actionable molecular targets remain limited in pediatric cases. Functional ex vivo drug-response assays may complement genom...
Precision medicine has expanded therapeutic options for rare central nervous system tumors, yet actionable molecular targets remain limited in pediatric cases. Functional ex vivo drug-response assays may complement genomic approaches by identifying tumor-specific sensitivities. Clival chordoma is a rare, locally aggressive tumor generally considered chemotherapy-refractory, particularly in children. We report the prospective use of a functional drug-response platform (Bioverso Test) to guide treatment in a pediatric patient with recurrent metastatic clival chordoma. A four-year-old patient with intracranial and pulmonary disease underwent testing using three-dimensional tumor microspheroids. The assay demonstrated broad resistance, with relative sensitivity to irinotecan (CPT-11). Treatment with an irinotecan-based regimen (50 mg/m²/day, days 1-5) resulted in a marked clinical and radiological response after three cycles, with significant reduction of intracranial and pulmonary lesions and no severe toxicities. The response has been sustained for 14 months. This case illustrates the clinical utility of integrating functional drug-response data into real-time decision-making, supporting a role for functional precision oncology in rare and treatment-refractory pediatric tumors.
Years of life lost in cutaneous squamous cell carcinoma: analysis of a prospective cohort of 1400 patients.
Dietz K, Eigentler TK, Breuninger H
J Cancer Res Clin Oncol · 2026 May · PMID 42184051 · Full text
PURPOSE: Cutaneous squamous cell carcinoma (cSCC) occurs predominantly in older adults. Disease-specific mortality is low, but conventional survival estimates do not capture the reduction in remaining life expectancy att...
PURPOSE: Cutaneous squamous cell carcinoma (cSCC) occurs predominantly in older adults. Disease-specific mortality is low, but conventional survival estimates do not capture the reduction in remaining life expectancy attributable to the disease. We therefore quantified years of life lost (YLL) in patients with cSCC overall and according to sex, age at diagnosis, progression, and risk profile. METHODS: We analysed 1400 prospectively evaluated patients with primary cSCC (median age 78 years) treated at the University Hospital Tübingen. Thirty-three patients died from cSCC, 493 died from other causes, and 874 were censored. Vital status was ascertained by annual queries to the public death registry, and death-certificate information was used to support cause-of-death classification. Patients were classified as at risk if desmoplasia, bone invasion, or immunosuppression was present. Expected remaining life expectancy was derived from German cohort life tables. YLL was estimated as the difference between expected life expectancy and observed survival using empirical and Weibull distributions adjusted for age and censoring. RESULTS: For the entire cohort, estimated YLL was 5.67 years; estimates were 5.30 years in men and 6.28 years in women. YLL was strongly influenced by age, sex, progression, and risk factors. In 70-year-old men, the estimated YLL was 7.7 years in patients with progression or risk factors and 2.5 years in those without. The corresponding estimates in women were 11.8 and 6.2 years. Although cSCC-specific mortality in the cohort was only 2.4%, the reduction in life expectancy was clinically relevant, particularly among women and high-risk patients. CONCLUSION: Years of life lost in cSCC increase in the presence of desmoplasia, bone invasion, immunosuppression, and tumor progression. YLL complements conventional survival measures and highlights a clinically meaningful disease burden despite low disease-specific mortality.
Molecular mechanisms of 5-FU resistance in colorectal cancer: the regulatory role of lncRNAs.
Bai B, Guo Y, Xie X … +1 more , Wang C
J Cancer Res Clin Oncol · 2026 May · PMID 42184042 · Publisher ↗
Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) that serve as key regulators of a variety of biological processes such as tumorigenesis and drug resistance. LncRNAs are more than 200 nucleotides in length and...
Long non-coding RNAs (lncRNAs) are non-coding RNAs (ncRNAs) that serve as key regulators of a variety of biological processes such as tumorigenesis and drug resistance. LncRNAs are more than 200 nucleotides in length and influence cancer progression by acting as miRNA sponges, regulating gene expression and promoting epigenetic changes. In colorectal cancer (CRC), lncRNAs promote 5-fluorouracil (5-FU) resistance by promoting DNA repair, inhibiting apoptosis, enhancing autophagy and epithelial-mesenchymal transition (EMT). Although most lncRNAs are upregulated in drug-resistant CRC cells, some lncRNAs act as inhibitors of tumor resistance. This article provides an overview of lncRNAs that play a role in mediating 5-FU resistance in colorectal cancer and their potential as biomarkers for predicting therapeutic efficacy.
Clinical significance of circulating FcγRIIa in the prognosis of patients with metastatic non-small cell lung cancer.
Wang X, Teng Y, Jiang M … +3 more , Zhao X, Yang X, Yue W
J Cancer Res Clin Oncol · 2026 May · PMID 42178410 · Publisher ↗
BACKGROUND: The tumor microenvironment plays a crucial role in determining the prognosis of tumors. Fc gamma receptor IIa (FcγRIIa), one of the three subtypes of FcγRII, is expressed on platelets and immunocytes such as...
BACKGROUND: The tumor microenvironment plays a crucial role in determining the prognosis of tumors. Fc gamma receptor IIa (FcγRIIa), one of the three subtypes of FcγRII, is expressed on platelets and immunocytes such as macrophages and neutrophils. These cellular elements collectively contribute to the tumor microenvironment. Previous research has indicated that FcγRIIa activates platelets and inflammatory cells, thus participating in tumor growth and metastasis. Nonetheless, limited information is available regarding FcγRIIa levels in most cancer types. This study aimed to detect serum FcγRIIa in 333 patients with non-small cell lung cancer (NSCLC) and 100 healthy individuals, and to explore the relationship between serum FcγRIIa levels and clinical outcomes in patients with NSCLC. METHODS: Serum samples from 333 patients with stage I-IV NSCLC and 100 healthy volunteers were analyzed using ELISA. The clinical and laboratory data underwent statistical analysis. RESULTS: Circulating FcγRIIa levels were markedly increased in patients with NSCLC, especially in advanced pathologic stages.ROC curve analysis yielded an AUC of 0.7713 (95% CI: 0.7132-0.8264), with an optimal cutoff value of 2115.88 pg/mL based on the Youden index (sensitivity: 60.06%, specificity: 86.00%). Notably, 13% of healthy controls showed FcγRIIa levels above the cutoff, suggesting that elevated FcγRIIa may partially reflect systemic inflammatory status. Survival analysis in 333 patients with NSCLC showed markedly shorter overall survival in FcγRIIa-positive cases. Serum FcγRIIa levels were further identified to be significantly associated with metastatic status. CONCLUSION: This study demonstrated that circulating FcγRIIa levels rise along with tumor progression and may serve as a potential complementary prognostic indicator in metastatic NSCLC, though these findings require validation in prospective cohorts with comprehensive adjustment for inflammatory markers and treatment regimens.
The burden of nasopharyngeal carcinoma in countries of the Association of Southeast Asian Nations (ASEAN), 1990-2023: findings from the Global Burden of Disease Study 2023.
Cheng L, Dong J, Li J
J Cancer Res Clin Oncol · 2026 May · PMID 42177696 · Publisher ↗
BACKGROUND: Nasopharyngeal carcinoma (NPC) remains a major cancer burden in parts of Asia, particularly in the Association of Southeast Asian Nations (ASEAN). However, the burden and trends within ASEAN have not been com...
BACKGROUND: Nasopharyngeal carcinoma (NPC) remains a major cancer burden in parts of Asia, particularly in the Association of Southeast Asian Nations (ASEAN). However, the burden and trends within ASEAN have not been comprehensively explored. METHODS: We extracted data on incidence, prevalence, mortality, and disability-adjusted life years (DALYs) of NPC in ASEAN from the Global Burden of Disease Study (GBD) 2023. We summarized absolute counts, crude rates, and age-standardized rates, and quantified temporal trends using estimated annual percentage changes (EAPCs). Analyses were stratified by sex, age group, and Sociodemographic Index (SDI). Associations between SDI and age-standardized rates were examined using Spearman correlation and smoothing spline models. RESULTS: In 2023, NPC in ASEAN accounted for 17,077 (95% UI: 12,742-22,109) incident cases, 65,845 (95% UI: 46,258-90,557) prevalent cases, 12,422 (95% UI: 9,657-15,413) deaths, and 435,087 (95% UI: 335,841-542,950) DALYs. Compared with 1990, the corresponding counts increased by 189%, 222%, 155%, and 141%, respectively. From 1990 to 2023, the age-standardized incidence and prevalence rate increased; whereas the age-standardized mortality rate declined slightly, and the age-standardized DALY rate remained stable. The burden was higher in males than in females and was concentrated in adults aged 45-59 years. Clear heterogeneity was observed across member states and SDI levels. CONCLUSIONS: NPC remains a major public health challenge in ASEAN. The overall burden continues to rise, with clear disparities between countries and higher impact among males and middle-aged adults. ASEAN countries should work together to reduce the regional burden of NPC.
Correlation of preoperative radiological lymph node assessment with pathological nodal and tumor findings in tongue and oral floor squamous cell carcinoma.
Ketschau J, Leonhardt Y, Leopold C … +8 more , Grabenhorst A, Singer H, Mohr J, Krautkremer N, Pippich K, Stimmer H, Wolff KD, Ritschl LM
J Cancer Res Clin Oncol · 2026 May · PMID 42176133 · Full text
PURPOSE: Preoperative imaging is central to cervical lymph node staging in oral squamous cell carcinoma (OSCC). However, the pathological and biological determinants underlying radiological lymph node suspicion remain po...
PURPOSE: Preoperative imaging is central to cervical lymph node staging in oral squamous cell carcinoma (OSCC). However, the pathological and biological determinants underlying radiological lymph node suspicion remain poorly defined. METHODS: This retrospective cohort study included 438 patients with OSCC of the tongue or floor of mouth treated with curative surgery and neck dissection between 2011 and 2021. Radiological lymph node assessment was classified using a three-level scale (unremarkable, suspicious, metastatic) and a dichotomous scale (unremarkable vs. suspicious/metastatic). Associations with patient characteristics, primary tumor features, and pathological nodal parameters were analyzed using univariable tests and multivariable ordinal logistic regression. A secondary model was performed in patients with available depth of invasion (DOI). RESULTS: Radiological lymph node assessment was strongly associated with pathological indicators of nodal tumor burden, including number of positive lymph nodes, lymph node ratio (LNR), extranodal extension (ENE), multilevel nodal involvement, and pathological N stage (all p < 0.001). In multivariate analyses, LNR emerged as the strongest independent predictor of radiological lymph node category, with increasing LNR associated with higher odds of radiological suspicion. Extranodal extension remained independently associated with radiological lymph node status. Depth of invasion showed a positive association that was attenuated after adjustment for nodal tumor burden, suggesting partial mediation. CONCLUSION: Radiological lymph node suspicion in OSCC primarily reflects cumulative nodal tumor burden and aggressive pathological features rather than isolated nodal involvement or patient-related factors. Radiological lymph node assessment may therefore serve as a surrogate marker of biologically aggressive nodal disease in clinical decision-making.
Ondansetron oral soluble pellicles vs. azasetron for preventing nausea and vomiting in patients receiving antitumor therapies: a comparative observational study.
Zhao C, Cao H, Yan S … +13 more , Sun R, Hu L, Yu H, Bai C, Cheng K, Wu X, Pan X, Zhang Q, Jiang B, Liu H, Tao S, Zhang J, Wang M
J Cancer Res Clin Oncol · 2026 May · PMID 42176039 · Publisher ↗
OBJECTIVE: Ondansetron oral soluble pellicles (OSP) show satisfactory effects on preventing nausea and vomiting following antitumor therapies. This study aimed to compare the antiemetic efficacy and safety profiles of on...
OBJECTIVE: Ondansetron oral soluble pellicles (OSP) show satisfactory effects on preventing nausea and vomiting following antitumor therapies. This study aimed to compare the antiemetic efficacy and safety profiles of ondansetron OSP vs. azasetron in patients receiving antitumor therapies. METHODS: A total of 110 patients who received antitumor therapies were included in this comparative observational study. According to patient willingness, disease status, and tolerance, 55 patients received ondansetron OSP, and the other 55 patients received intravenous azasetron. During acute and delayed phases, the function living index emesis (FLIE) scale score and degrees of nausea and vomiting [high (46-63 points), moderate (19-45 points), or low (0-18 points)] were assessed. Adverse reactions were collected. RESULTS: During the acute phase, FLIE-nausea (5.7 ± 8.9 vs. 17.9 ± 13.6) and vomiting (6.9 ± 7.8 vs. 17.6 ± 13.9) domain scores were lower in patients receiving ondansetron OSP than those receiving azasetron (both P < 0.001). The degrees of nausea and vomiting were lower in patients receiving ondansetron OSP than those receiving azasetron (both P < 0.05). During the delayed phase, FLIE-nausea (5.0 ± 7.9 vs. 10.8 ± 9.1) and vomiting (4.2 ± 6.6 vs. 9.2 ± 8.7) domain scores were lower in patients receiving ondansetron OSP than those receiving azasetron (both P < 0.001). Regarding adverse reactions, the incidence of constipation was lower in patients receiving ondansetron OSP than those receiving azasetron (7.3% vs. 30.9%) (P = 0.003), but the incidence of headache did not differ (P = 0.113). CONCLUSION: Ondansetron OSP possess superior antiemetic effects and safety profiles to azasetron in patients receiving antitumor therapies.
Hypoxia-induced endoplasmic reticulum stress mediates lenvatinib resistance in hepatocellular carcinoma through the IRE1α-XBP1s-HIF1α pathway.
Zhang C, Jiang Y, Liu J … +2 more , Sun G, Yu H
J Cancer Res Clin Oncol · 2026 May · PMID 42165895 · Publisher ↗
BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, with a dismal prognosis for advanced patients. Lenvatinib, a first-line anti-angiogenic agent, has improved clinica...
BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths globally, with a dismal prognosis for advanced patients. Lenvatinib, a first-line anti-angiogenic agent, has improved clinical outcomes, but drug resistance remains a major unmet clinical need. Hypoxia, a hallmark of solid tumors, crosstalks with endoplasmic reticulum stress (ERS), yet their combined role in lenvatinib resistance in HCC remains undefined. METHODS: TCGA and GEO datasets were analyzed for ERS-related gene expression and prognostic value. In vitro experiments were conducted in HepG2 and HCCLM3 cells under normoxic (21% O₂) or hypoxic (1% O₂) conditions. Cell viability, apoptosis, migration, and protein expression were assessed via standard assays. siRNA silencing and the ERS inhibitor 4-PBA were used for mechanistic validation. RESULTS: The ERS marker GRP78 was significantly upregulated in HCC tissues and correlated with poor survival. Hypoxia induced ERS in HCC cells, promoting proliferation and migration while attenuating lenvatinib-induced apoptosis. Mechanistically, hypoxia induces activation of the IRE1α-XBP1s-HIF1α axis, and genetic silencing of this axis restores lenvatinib sensitivity. 4-PBA effectively reversed hypoxia-mediated drug resistance. CONCLUSIONS: Hypoxia-induced ERS mediates lenvatinib resistance in HCC via the IRE1α-XBP1s-HIF1α pathway. Targeting this axis provides a promising strategy to overcome anti-angiogenic therapy resistance in HCC.
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