J Cancer [JOURNAL]
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200 papers
Targeting Dermatologic Side Effects of Immunotherapy Using Novel Skin Care Products.
Claes M, Lodewijckx J, Robijns J … +9 more , Tuts L, Lenaerts M, Vandaele E, Wessels T, Requilé A, Luyten D, Verheezen Y, Joosens E, Mebis J
J Cancer · 2026 · PMID 41584033 · Full text
Immunotherapy can be accompanied by cutaneous adverse events that negatively impact the patient's quality of life (QoL). This trial aimed to evaluate the efficacy of two novel skin care products in preventing and managin...
Immunotherapy can be accompanied by cutaneous adverse events that negatively impact the patient's quality of life (QoL). This trial aimed to evaluate the efficacy of two novel skin care products in preventing and managing cutaneous adverse events associated with immunotherapy. An interventional, open-label, single-group, pretest-posttest study was conducted at the Jessa Hospital (Belgium) involving cancer patients receiving immunotherapy (n=75). Patients applied the skin care products daily for three weeks. A researcher evaluated skin toxicity using the National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0. Questionnaires assessed the frequency and severity of their symptoms (Numeric Rating Scale, NRS), the patient's QoL (Dermatology Life Quality Index, DLQI, and Skindex-29), the Patient Benefit Index, and patient satisfaction (NRS). The CTCAE and NRS showed that pruritus and xerosis were the most frequently observed skin toxicities. According to the NCI-CTCAE, an improvement was detected in the grade of pruritus and xerosis after applying the novel emollients (P<0.001). All patient-reported symptoms decreased significantly in frequency. Both the Skindex-29 total score (P<0.001) and DLQI (P=0.038) improved over time. Moreover, 42.7% of the patients experienced at least one patient-relevant benefit of the treatment. Lastly, 70.7% of the patients were satisfied with the products, and 74.6% would recommend them to other patients. This trial demonstrates that the two novel emollients effectively alleviate immunotherapy-related dermatological toxicities. As a result, an improvement in the patient's QoL was observed, accompanied by high satisfaction and a strong likelihood of recommendation. Future research with a control group is necessary to draw firm conclusions.
Cuproptosis-related gene PROK1 predicts the diagnosis and prognosis of prostate cancer based on multiple machine learning.
Qin X, Wang Q, Jiang W … +12 more , Zhao Y, Li H, Zi T, Zhu Y, Li X, Xu C, Yang T, Wang X, Yao Y, Chen X, Zhou J, Wu G
J Cancer · 2026 · PMID 41584032 · Full text
Cuproptosis, a newly identified form of cell death, influences the development, progression, and prognosis of prostate cancer (PCa). Identifying key genes associated with cuproptosis and developing robust predictive mode...
Cuproptosis, a newly identified form of cell death, influences the development, progression, and prognosis of prostate cancer (PCa). Identifying key genes associated with cuproptosis and developing robust predictive models through machine learning approaches are crucial for personalized PCa treatment. In our study, multiple machine learning methods and their combinations were employed for the construction of diagnostic and prognostic models for PCa, which were then validated in multiple external independent cohorts. The model key gene, PROK1, was selected for further analysis, and its expression was compared in clinical samples and cell lines. Additionally, the anticancer effect of PROK1 was explored through regulating the expression of PROK1. Most cuproptosis-related genes (CRGs) showed differential expression between PCa and normal prostate tissues. The two clusters derived from the Consensus Clustering method, based on cuproptosis gene expression characteristics, exhibit distinct clinical features and immune microenvironment infiltration patterns. Models constructed based on machine learning methods showed promising diagnostic capabilities for PCa and were associated with the prediction of biochemical recurrence-free survival and disease-free survival of patients. Inhibiting PROK1 expression promoted PCa cell proliferation and invasion, while its overexpression had the opposite effect. Furthermore, pathway exploration revealed that PROK1 inhibits tumor growth by mediating apoptosis under copper ion stress. Its association with cuproptosis warrants further investigation to elucidate the precise mechanism.
Biomarkers for Recurrence and Prognosis in Metastatic Urothelial Cancer: Emerging Clinical Applications.
Cendra AS, Ospino LR, Pekarek L … +15 more , Dbouk Y, Chnaiker S, Luengo A, Villamor T, Corralo A, Diaz-Pedrero R, Lopez-Gonzalez L, Saez MA, Alhaddadin MNM, Alonso-Bartolome MB, Casanova-Martín C, Alvarez-Mon M, Rodriguez LG, Barrena-Blázquez S, Ortega MA
J Cancer · 2026 · PMID 41438588 · Full text
Urothelial cancer (UC) remains a highly recurrent and heterogeneous malignancy in which reliable biomarkers for recurrence and prognosis are needed, particularly in the metastatic setting. In recent years, the identifica...
Urothelial cancer (UC) remains a highly recurrent and heterogeneous malignancy in which reliable biomarkers for recurrence and prognosis are needed, particularly in the metastatic setting. In recent years, the identification and validation of biomarkers have become an essential pillar for improving the diagnosis, monitoring, and prognosis of this disease. This review summarizes and analyzes recent advances in the study of serological, urinary, histological, genetic, and microRNA biomarkers, as well as emerging tools such as circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA). Together, these non-invasive markers show significant potential to complement conventional diagnostic techniques, optimize risk stratification, and support a more personalized therapeutic approach. Furthermore, the integration of new sequencing technologies and liquid biopsy methods is opening new perspectives for the early detection of recurrence and the dynamic assessment of treatment response. However, the routine clinical implementation of these biomarkers still requires validation through standardized prospective studies.
Cancer Cell Dormancy and Chemotherapy Resistance.
Hu J, Zhou W, Zhao Y … +5 more , Li P, Zhao Z, Wang W, Wang W, Wang Y
J Cancer · 2026 · PMID 41438587 · Full text
Cancer cell dormancy is associated with tumor recurrence and metastasis. Chemotherapy usually induces dormancy as external pressure on the tumor. Dormant cells have considerable resistance to antitumor drugs, although th...
Cancer cell dormancy is associated with tumor recurrence and metastasis. Chemotherapy usually induces dormancy as external pressure on the tumor. Dormant cells have considerable resistance to antitumor drugs, although they are not harmful to the host if they do not wake up. Chemotherapy induces a dormant phenotype through remodeling of the tumor microenvironment and alteration of intracellular signaling networks. Multiple adaptive mechanisms that confer drug resistance have been identified in these dormant cells, including the unfolded protein response to endoplasmic reticulum stress, metabolic reprogramming favoring oxidative phosphorylation to avoid damage from oxidative stress, and autophagy to realize the circular utilization of energy. However, dormancy is reversible. The conversion between dormancy and awakening of the tumor during chemotherapy and the recovery period after treatment is modulated by several factors, including the dose and cycle of treatment, and individual differences among patients. The direct elimination of cancer cells or permanent dormancy by chemotherapy predicts favorable outcomes. According to this theory, understanding the mechanisms of cancer dormancy and awakening under chemotherapy and improving prognosis using suitable treatment strategies requires further investigation. This review analyzed studies on cancer cell dormancy and response to chemotherapy to identify potential novel interests for future studies and probable strategies to optimize chemotherapy in clinical trials.
Loss of is a Hallmark of RTK II Glioblastomas.
Langwieder CK, Hölzl D, Hutarew G … +5 more , Schlicker HU, Alinger-Scharinger B, Schwartz C, Sotlar K, Kraus TFJ
J Cancer · 2026 · PMID 41438586 · Full text
Glioblastomas represent the most prevalent primary brain tumors in adults. Due to their highly malignant biological behavior, they are classified as grade 4 according to the World Health Organization (WHO) classification...
Glioblastomas represent the most prevalent primary brain tumors in adults. Due to their highly malignant biological behavior, they are classified as grade 4 according to the World Health Organization (WHO) classification of brain tumors. Despite the progress in understanding the molecular pathogenesis of these tumors, no curative therapy has been developed for patients with glioblastoma. In this study, an integrated comparative analysis of chromosomal deletion was performed on 45 glioblastomas, representing the most frequent molecular subtypes of glioblastomas, receptor tyrosine kinase (RTK) I (n=13), RTK II (n=15), and the mesenchymal subtype (MES) (n=17). The analysis of copy number variation (CNV) profiles was conducted on losses. Subsequent statistical analysis was then applied to correlate the collected data with molecular glioblastoma epigenotypes. Loss of was found 44% (20/45) of all glioblastomas, thereby, in 46% (6/13) of RTK I, 67% (10/15) RTK II, and 24% (4/17) of MES. Statistical analysis showed that loss of is significant (p < 0.01) in RTK II compared with MES. Even though does not per se function as a molecular target, there is great potential for enhancing treatment outcomes through the restoration of the tumor-suppressing capabilities of . This strategy can be employed in therapeutic interventions and is a promising avenue for research. This efficacy of this approach demonstrates high potential, as evidenced by its efficacy in other tumors, including melanoma.
Multi-Omics and Single-Cell Dissection of Exostosin Glycosyltransferases (EXT1/EXT2) Reveals Divergent Oncogenic Roles and Therapeutic Vulnerabilities in Gliomas.
Chiang YC, Wang CY, Palekkode N … +22 more , Yang SF, Chang KF, Ko CC, Chang CH, Lin HR, Wu CJ, Ho YC, Lin CC, Yuan CH, Kumar S, Solomon DD, Ngadio JL, Wulandari FS, Xuan DTM, Hsieh CB, Yen MC, Yeh IJ, Ko PC, Shih CL, Chan HB, Lee YK, Nguyen NUN
J Cancer · 2026 · PMID 41438585 · Full text
Exostosin glycosyltransferase 1 () and exostosin glycosyltransferase 2 () catalyze heparan sulfate chain elongation and are increasingly implicated in cancer biology, but their roles in gliomas remain incompletely define...
Exostosin glycosyltransferase 1 () and exostosin glycosyltransferase 2 () catalyze heparan sulfate chain elongation and are increasingly implicated in cancer biology, but their roles in gliomas remain incompletely defined. Here, we performed an integrative multi-omics analysis to dissect the transcriptional, epigenetic, and microenvironmental landscape of and across gliomas. Bulk transcriptomic data from The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) revealed that both EXT1 and EXT2 are upregulated in high-grade gliomas and associate with adverse survival, with EXT1 showing the strongest and most consistent prognostic impact. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) indicated that EXT1-high tumors are enriched for DNA damage and replication stress programs, cell cycle progression, inflammatory response, and stromal activation pathways, whereas EXT2 expression is preferentially linked to extracellular matrix remodeling, cytoskeletal organization and angiogenesis-related signaling. Single-cell RNA sequencing and Immune deconvolution using Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts (CIBERSORT) and Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) showed that correlates with increased stromal and immune scores, and reduced cytotoxic T cell signatures, consistent with an immunosuppressive tumor microenvironment. expression is enriched in gliomas with pronounced vascular and mesenchymal features, supporting a complementary role in invasive growth and tissue remodeling. Immunohistochemistry on a glioma tissue microarray validated the upregulation of protein in high-grade tumors. The study findings identified as a central glycosylation-linked regulator of replication stress tolerance and immune remodeling in gliomas, and suggest that contributes to extracellular matrix and cytoskeletal reprogramming. The exostosin axis represents a promising source of prognostic biomarkers and potential therapeutic targets in glioma.
Identification of key ferroptosis-related targets in colorectal cancer: A transcriptomics-driven study via machine learning and AUcell analysis of single-cell RNA-sequencing.
Liang Z, Hou Z, Yu Z … +5 more , Zeng B, Li F, Wu J, Li Y, Jiang Z
J Cancer · 2026 · PMID 41438584 · Full text
Colorectal cancer (CRC) has emerged as the third most prevalent malignancy worldwide. The pursuit of dependable molecular signatures stands as a crucial endeavor for tailoring treatment approaches, refining prognostic as...
Colorectal cancer (CRC) has emerged as the third most prevalent malignancy worldwide. The pursuit of dependable molecular signatures stands as a crucial endeavor for tailoring treatment approaches, refining prognostic assessments, and heightening therapeutic efficacy in CRC management. This investigation was conducted to elucidate essential genes and molecular mechanisms associated with ferroptosis in CRC through implementing machine-learning approaches and AUcell analysis. The GEO repository and FerrDb served as primary sources for extracting information of gene sets on colorectal cancer and iron-dependent cell death mechanisms. To determine potential therapeutic targets with biomarker significance, we implemented LASSO and SVM-RFE methodology. The immune infiltrates were characterized followed by a competing endogenous RNA network analysis. The AUCell R package was utilized to examine the targeted gene activity patterns within individual cell lines using single-cell transcriptome data. The qRT-PCR and Human Protein Atlas (THPA) database were used to validate the expression of target genes. Potential therapeutic were explored through the DGIdb database. Through the application of machine learning methodologies, five genes were identified as pivotal biomarker candidates: AQP8, NOX4, NR5A2, SCD, and TIMP1. The result of AUcell algorithm showed that the distribution of AUC values exhibited a bimodal pattern, with 2733 cells demonstrating elevated AUC values above the threshold of 0.091. The result of qRT-PCR showed that NOX4, SCD, and TIMP1 were significantly upregulated, while the expression of AQP8 and NR5A2 did not exhibit the expected differences. Both mRNA and IHC analyses from HPA database confirmed the abnormal expression of these pivotal candidate biomarkers. Algorithmic assessment via CIBERSORT methodology revealed notable shifts in immune cell composition within the tumor microenvironment of individuals diagnosed with CRC. Furthermore, A competing endogenous RNA network and 51 potential drug candidates were identified. A systematic framework implementing machine-learning approaches and AUcell analysis was established for identifying core ferroptosis genes and validating their functional link to ferroptosis. Meanwhile, a reliable ferroptosis-associated signature was established, which shed new light on the ferroptosis-mediated molecular mechanisms and therapeutic potential underlying CRC.
Immunomodulatory Protein (GMI) Enhances Phagocytosis by Suppressing STAT3/CD47 Signaling in EGFR-Mutant NSCLC Resistant to Gefitinib and Osimertinib.
Hsieh YC, Hsin IL, Chiu LY … +6 more , Hung YC, Kang YT, Chang HY, Lin CH, Ko JL, Liu YF
J Cancer · 2026 · PMID 41438583 · Full text
Target therapy is effective for epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC). However, resistance often occurs after treatment for several months. Macrophages have difficulty in...
Target therapy is effective for epidermal growth factor receptor (EGFR) mutation in non-small cell lung cancer (NSCLC). However, resistance often occurs after treatment for several months. Macrophages have difficulty in devouring resistant cells. immunomodulatory protein (GMI) exhibits anti-tumour and immunomodulatory activities. This study aimed to investigate whether GMI overcomes Osimertinib (Tagrisso) and Gefitinib (Iressa) resistance via enhancing macrophage polarization. GMI attenuated signal transducer and activator of transcription 3 (STAT3) phosphorylation and downstream CD47 expression in parental and resistant cells via Western blot and RT-qPCR. Overexpressed STAT3 restored GMI-induced apoptosis and GMI-reduced transcription of CD47 in HCC827 and H1975 lung cancer cells. Phospho-STAT3 inhibitor (W1131) also reduced the expression of CD47 in NSCLC cells. The interaction between GMI and W1131 was effective in reducing phosphorylated STAT3 and CD47. ImageXpress Pico analysis revealed that GMI enhanced phagocytotic activity of macrophages toward tumour cells with Red CMTPX and Green CMFDA dyes. The results showed that GMI enhanced macrophage phagocytosis of lung cancer cells by inhibiting STAT3 and reducing CD47 expression. In addition, GMI enhanced M1 inhibition of M2 polarization but had no effect on M1 differentiation. This is the first study to demonstrate that GMI enhances macrophage phagocytosis and modulates the STAT3-CD47 axis to overcome EGFR-TKI resistance in NSCLC, highlighting its potential as a novel adjunct immunotherapeutic agent.
Comprehensive characterization of AP-1 adaptor complex genes in lung cancer reveals AP1AR as a novel prognostic and therapeutic biomarker.
Solomon DD, Yeh IJ, Liu HL … +11 more , Su CY, Lee YK, Ko CC, Lin HR, Kumar S, Xuan DTM, Palekkode N, Fathima A, Lin HY, Wang CY, Yen MC
J Cancer · 2026 · PMID 41438582 · Full text
Lung cancer remains the leading cause of cancer mortality. The AP-1 adaptor complex, including AP1AR, AP1S1, AP1S2, AP1S3, AP1M1, AP1M2, AP1B1, and AP1G1, functions as a conserved hub of vesicular trafficking, selecting...
Lung cancer remains the leading cause of cancer mortality. The AP-1 adaptor complex, including AP1AR, AP1S1, AP1S2, AP1S3, AP1M1, AP1M2, AP1B1, and AP1G1, functions as a conserved hub of vesicular trafficking, selecting cargo and coordinating clathrin-mediated transport. By shaping receptor recycling, membrane composition, and signal duration, AP-1 influences core cancer phenotypes such as proliferation, migration, and therapy response. However, the family-level role of AP-1 adaptors in lung cancer is incompletely defined. We systematically profiled all eight AP-1 adaptor genes using multi-omics datasets, survival resources, pharmacogenomic panels, Human Protein Atlas data, pathway enrichment, and single-cell RNA sequencing with cell-cell communication modeling. was consistently upregulated in lung adenocarcinoma and independently associated with poorer overall survival. It was linked to cell-cycle progression, DNA replication checkpoints, hypoxia, and epithelial-to-mesenchymal transition (EMT). At single cell resolution, also regulate malignant epithelial and fibroblast cell types. Pseudotime analyses revealed progressive activation along proliferative and EMT axes, and CellChat modeling indicated enhanced stromal and epithelial signaling. and showed complementary roles, associated with oncogenic/inflammatory signaling and immune-metabolic programs, respectively. These findings identify as a clinically relevant biomarker and highlight AP-1 adaptor biology as an underexplored contributor to lung adenocarcinoma progression and therapeutic stratification.
Disulfiram/Copper Combination as a Potential Therapeutic Approach for Hepatocellular Carcinoma: Targeting the ATF3-Mitochondrial Cell Death Pathway.
Cao J, Deng J, Li X … +5 more , Chen Y, Wang J, Chong Y, Gong J, Lin B
J Cancer · 2026 · PMID 41438581 · Full text
Hepatocellular carcinoma (HCC) represents a major public health issue globally, necessitating the urgent development of new therapies. The therapeutic efficacy of disulfiram (DSF) and copper (Cu) in HCC was investigated...
Hepatocellular carcinoma (HCC) represents a major public health issue globally, necessitating the urgent development of new therapies. The therapeutic efficacy of disulfiram (DSF) and copper (Cu) in HCC was investigated in the present study, focusing on cytotoxicity, mitochondrial function, and apoptosis to clarify the mechanistic basis of this drug combination. Our findings revealed a significant, dose-dependent reduction in HCC cell viability with DSF/Cu treatment. Further investigation showed increased reactive oxygen species (ROS) levels, decreased adenosine triphosphate (ATP) production, and a decline in mitochondrial membrane potential (MMP). These events culminated in the activation of caspase-9 and caspase-3, key enzymes in the apoptotic pathway, leading to cell death. Mechanistically, DSF/Cu synergistically increased the expression of activating transcription factor 3 (ATF3), a known tumor suppressor, in HCC cells. studies using a mouse tumor model supported these findings, demonstrating significantly inhibited tumor growth in the DSF/Cu group compared with the control group. Overall, our study findings suggest that the DSF/Cu combination exhibits significant therapeutic potential against HCC by modulating the ATF3-dependent mitochondrial apoptosis pathway, a strategy that warrants further preclinical exploration.
Molecular Signature of Cisplatin Resistance in Ovarian Cancer Identifies Therapeutic Opportunities for Re-sensitization.
Mansour M, van Ginkel S, Alata M … +2 more , Bani I, Elhussin I
J Cancer · 2026 · PMID 41438580 · Full text
Cisplatin remains a standard first-line therapy for epithelial ovarian cancer; however, chemoresistance leads to poor prognosis and high recurrence. Analysis of The Cancer Genome Atlas confirmed improved overall survival...
Cisplatin remains a standard first-line therapy for epithelial ovarian cancer; however, chemoresistance leads to poor prognosis and high recurrence. Analysis of The Cancer Genome Atlas confirmed improved overall survival in cisplatin-sensitive tumors, underscoring the need for strategies to overcome resistance in clinical settings. Integrative bioinformatics of cisplatin-treated ovarian cancer datasets from the Gene Expression Omnibus (n=255) identified six molecular drivers of resistance: Kaiso (ZBTB33), pregnane X receptor (PXR), NF-κB, HER2 (ERBB2), P-glycoprotein (P-gp/ABCB1), and HIF1A. These targets were validated in ovarian tumor specimens via immunohistochemistry, confirming elevated expression in chemo-resistant disease. Additionally, the quantitative real-time PCR analysis confirms the transcriptional upregulation of the six resistance-associated genes in cisplatin-resistant SKOV3 and OVCAR-5 ovarian cancer cells, consistent with the immunohistochemistry findings. The average fold change in mRNA transcripts ranged from 2.4 for P-glycoprotein to 5 for both NF-kB and Kaiso. Although less well studied in ovarian cancer, Kaiso is known to regulate EMT and tumor invasion in other solid tumors. Functional studies using SKOV3 and OVCAR-5 cell lines demonstrated that knockdown of Kaiso via RNA interference significantly increased cisplatin-induced cell death, indicating a direct role in therapeutic resistance. Furthermore, we investigated the synergistic effects of combining stearidonic acid (SDA), a plant-based omega-3 fatty acid known to inhibit NF-κB, with cisplatin on cell death in SKOV3 and OVCAR-5 cell lines, and compared the results with those of each compound used individually. Interestingly, co-treatment with stearidonic acid (SDA) synergistically enhanced the cytotoxicity of cisplatin at a lower dose in both cell models. These findings reveal a clinically relevant resistance signature and highlight the therapeutic potential of combinatorial strategies that target both transcriptional regulators (e.g., Kaiso) and inflammatory signaling (e.g., NF-κB). Dual targeting of these pathways may resensitize tumors to cisplatin and improve outcomes for patients with advanced ovarian cancer.
CES3 promotes NSCLC progression via lipid metabolic reprogramming regulated by TFAP2A.
Luo P, Huang Z, Ding S … +7 more , Tang Z, Wei Y, Jiang S, Tang R, Li F, Yang H, Zhao L
J Cancer · 2026 · PMID 41438579 · Full text
Metabolic reprogramming is an important feature in non-small cell lung cancer (NSCLC) that can result in therapeutic resistance. Exploring dysregulated lipid metabolism in NSCLC will accelerate the development of potenti...
Metabolic reprogramming is an important feature in non-small cell lung cancer (NSCLC) that can result in therapeutic resistance. Exploring dysregulated lipid metabolism in NSCLC will accelerate the development of potential lipid biomarkers to target and control the malignant progression of NSCLC. In this study, RNA next-generation sequencing of 25 paired NSCLC specimens and adjacent normal tissues was used to find that carboxylesterase 3 (CES3) was upregulated in NSCLC. Knockdown of CES3 significantly inhibited NSCLC cell proliferation and invasion. Additionally, CES3 inhibition promoted lipid accumulation in NSCLC cells. Furthermore, we found transcription factor AP-2α (TFAP2A) could regulate CES3 levels in NSCLC. TFAP2A was found upregulated in NSCLC and correlated with poorer outcome. Inhibiting TFAP2A resulted in suppressed cell proliferation as well as invasion while increasing the lipid accumulation in NSCLC. CES3 overexpression could reverse the impact of TFAP2A inhibition on NSCLC progression. In summary, TFAP2A dysregulation resulted in CES3 overexpression and the following NSCLC tumorigenesis. Targeting the TFAP2A/CES3 axis may represent a promising therapeutic strategy for NSCLC in the future.
Association of Ion Concentration with Immune-Related Adverse Events and Prognosis in Lung Cancer Patients Treated with PD-1/PD-L1 Inhibitors.
Liao CW, Chen J, Liu JS … +5 more , She L, Zou T, Wang Y, Wang Z, Liu ZQ
J Cancer · 2026 · PMID 41438578 · Full text
: irAEs were associated with immunotherapy response in cancer treatment, but severe irAEs discontinued immunotherapy and affected the quality of life. This study aimed to identify ion concentrations as potential biomarke...
: irAEs were associated with immunotherapy response in cancer treatment, but severe irAEs discontinued immunotherapy and affected the quality of life. This study aimed to identify ion concentrations as potential biomarkers for irAEs and prognosis in lung cancer patients receiving ICI therapy. A retrospective analysis was conducted on 459 lung cancer patients who received ICI treatment at Xiangya Hospital from April 2019 to May 2023. Patient characteristics, ion concentrations (K, Na, Cl, Ca, PO and Mg), irAEs, and prognosis were systematically collected. Univariable and multivariable regression analyses, including binary logistic regression and Cox regression models, were employed to identify factors associated with irAEs and PFS. Among 459 lung cancer patients receiving ICI treatment, 378 (82.4%) of the patients suffered irAEs. PD-L1 expression, ICI cycles, ORR and DCR were linked to irAEs occurrence. Cardiotoxicity, hypothyroidism, and dermatoxicity were the predominant irAEs types, but mostly mild to moderate. Notably, elevated potassium (K) level was significantly correlated with both a higher risk of irAEs and longer PFS. The findings suggest that K concentration prior to initiating treatment with ICIs may be a biomarker of irAEs and PFS in lung cancer patients.
Sulforaphane-cysteine elicits apoptosis through JNK-mediated caspase activation in oral squamous cell carcinoma cells.
Chen YL, Chen YT, Yang WE … +5 more , Su CW, Tsai MY, Su SC, Yang SF, Lin CW
J Cancer · 2026 · PMID 41438577 · Full text
Sulforaphane-cysteine (SFN-Cys) is a naturally-occurring form of plant-derived isothiocyanate metabolites that displays several tumor-suppressive properties. However, the oncostatic potential of SFN-Cys on oral squamous...
Sulforaphane-cysteine (SFN-Cys) is a naturally-occurring form of plant-derived isothiocyanate metabolites that displays several tumor-suppressive properties. However, the oncostatic potential of SFN-Cys on oral squamous cell carcinoma (OSCC) is mostly elusive. In this study, we tried to test whether SFN-Cys affects OSCC to progress and further explored the underlying array of molecular cues that SFN-Cys mediates. Our results demonstrate that SFN-Cys was an effective inducer of cytotoxicity to OSCC cells, accompanied with blockage of cell cycling and promotion of apoptotic events. Moreover, treatment of OSCC cells with SFN-Cys attuned an apoptosis-associated protein regulatory program, underlined by downregulation of apoptosis suppressors (cIAP-1 and XIAP) and activation of caspase cascades. Furthermore, caspase activations in SFN-Cys-treated OSCC cells were affected by the pre-incubation with a specific c-Jun N-terminal kinase (JNK) inhibitor, suggesting a functional link of JNK pathway to SFN-Cys's actions in OSCC cells. Collectively, our data revealed that SFN-Cys hampered cell cycle progression and elicited apoptotic responses in OSCC via a JNK-mediated activation of caspase pathways. These findings provide possible avenues for the application of a natural compound in the management of oral malignancies.
Interleukin-17 receptor A drives cancer stem-like properties in colorectal cancer through STAT3 activation.
Jiang JK, Lin CH, Lin CC … +6 more , Lo LC, Sung PY, Wen ZY, Lin CP, Chang TA, Yang CY
J Cancer · 2026 · PMID 41438576 · Full text
Cancer stem cells (CSCs) play pivotal roles in tumor relapse, metastasis, and therapy resistance. Interleukin 17 receptor A (IL-17RA) is a key mediator in colorectal cancer (CRC) pathogenesis and progression. Our recent...
Cancer stem cells (CSCs) play pivotal roles in tumor relapse, metastasis, and therapy resistance. Interleukin 17 receptor A (IL-17RA) is a key mediator in colorectal cancer (CRC) pathogenesis and progression. Our recent study demonstrated that reduced IL-17RA expression correlates with favorable prognosis in CRC patients and suppresses tumor growth in murine models. This study aimed to investigate the role of IL-17RA in promoting cancer stem-like properties and its impact on colorectal cancer prognosis and chemoresistance. Expression levels of IL-17RA and CSC markers in CRC cells were evaluated using quantitative real-time polymerase chain reaction and Western blotting. Kaplan-Meier analysis of 68 CRC patients revealed that high IL-17RA expression is associated with poor clinical outcomes. To investigate IL-17RA's functional role, CRC cells with stable IL-17RA overexpression were analyzed for changes in CSC marker expression, sphere formation, and 5-fluorouracil (5-FU) resistance. IL-17RA overexpression significantly increased CSC marker expression, including cluster of differentiation 133 (CD133), leucine-rich repeat-containing G protein-coupled receptor 5 (LGR5), sex determining region Y-box 2 (SOX2), and enhanced tumor sphere formation and 5-FU resistance in SW620 cells. Specific inhibitors of IL-17RA signaling, such as the STAT3 inhibitor Stattic, reduced the expression of CD133, LGR5, ALDHA1, SOX2 and c-MYC, as well as tumor sphere formation in SW620 cells. These findings elucidate a novel IL-17RA-STAT3 axis that regulates CSC properties in CRC and highlight IL-17RA as a promising prognostic biomarker and therapeutic target for CRC treatment.
The Role of Inflammatory Biomarkers in PIPAC: Predicting Survival and Treatment Completion in Patients with Peritoneal Metastasis.
Roensholdt S, Graversen M, Detlefsen S … +3 more , Fristrup C, Pfeiffer P, Mortensen MB
J Cancer · 2026 · PMID 41438575 · Full text
Appropriate patient selection is essential for optimising outcomes in individuals with peritoneal metastasis (PM) undergoing treatment with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). This study investigate...
Appropriate patient selection is essential for optimising outcomes in individuals with peritoneal metastasis (PM) undergoing treatment with Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC). This study investigated the prognostic value of pretreatment inflammatory biomarkers and explored their ability to predict the possibility of completion of three or more PIPAC treatments. This observational study analysed prospectively collected data from patients with PM of gastrointestinal or ovarian origin enrolled in the PIPAC OPC-1 or OPC-2 studies between March 2015 and January 2022. Six biomarkers were examined: Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio, Systemic Immune-Inflammation Index (SII), C-reactive protein, modified Glasgow Prognostic Score, and Prognostic Nutritional Index. Biomarkers were obtained pretreatment, and treated as continuous variables. Survival was assessed using Kaplan-Meier and Cox regression analyses, adjusting for covariates available prior to the first PIPAC. ROC analysis was used to evaluate the predictive performance. A p-value less than 0.05 was considered statistically significant. The cohort consisted of 130 patients, with a median overall survival (OS) of 8.7 months. Sixty percent of the patients received three or more PIPAC treatments. Elevated levels of all six biomarkers were significantly associated with reduced OS. In the multivariate analysis, five biomarkers remained independently associated with survival. NLR and SII demonstrated moderate discriminatory power (AUC > 0.70) for predicting the completion of three or more treatments. Pretreatment inflammatory biomarkers are objective, readily accessible and clinically applicable tools that may support the selection of appropriate candidates for PIPAC. The findings of this study encourage the integration of biomarker assessments into future PIPAC research protocols.
Macrophages in Colorectal Cancer: from Normal Mucosa to Distant Metastasis: Beyond the M1/M2 Paradigm.
Pavlov S, Ali E, Ambrozkiewicz F … +5 more , Ye W, Rajtmajerová M, Liška V, Hemminki K, Trailin A
J Cancer · 2026 · PMID 41438574 · Full text
Colorectal cancer (CRC) is the third most common malignancy and leading cause of mortality worldwide. Tumor microenvironment (TME) strongly influences CRC growth, immune evasion, and metastasis. Among various immune cell...
Colorectal cancer (CRC) is the third most common malignancy and leading cause of mortality worldwide. Tumor microenvironment (TME) strongly influences CRC growth, immune evasion, and metastasis. Among various immune cells, tumor-associated macrophages (TAMs) act as key regulators of cancer progression. Although traditionally classified as M1 (pro-inflammatory, anti-tumor) or M2 (anti-inflammatory, pro-tumor), single-cell RNA sequencing and spatial transcriptomics have revealed that macrophage phenotypes exist along a continuum, challenging the classic dichotomy. This review investigates macrophages throughout CRC development, from normal mucosa to adenoma, primary tumor, and liver metastasis. Early adenomas feature M1-like macrophages that drive local inflammation, whereas advanced adenomas and invasive CRC comprise M2-like macrophages promoting angiogenesis, extracellular matrix remodeling, and immunosuppression. TAMs are crucial in CRC metastasis, particularly to the liver. M2-polarized Kupffer cells express CD206 and CD163, secrete hepatocyte growth factor, and activate PI3K/AKT signaling, thus aiding extravasation, survival, and proliferation of metastatic cells. They also foster lymphangiogenesis and immunosuppression through release of IL-10 and TGF-β. CRC's consensus molecular subtype (CMS) impacts the profile of TAMs: CMS1 (microsatellite instability-high) tumors typically harbor an anti-tumor M1 macrophages, while CMS4 (mesenchymal) tumors are enriched in M2-like TAMs, which facilitate stromal remodeling and angiogenesis, ultimately contributing to a poor prognosis. Spatial distribution also matters. Abundant M1 macrophages at the invasive margin correlate with better outcomes, whereas M2 macrophages in tumor centers and metastatic sites drive disease progression. Some CD206+ macrophages, however, support vascular normalization, which can limit metastasis. These findings underscore the complexity of TAMs in CRC and highlight the necessity of multi-marker phenotyping. Given the limitations of the M1/M2 paradigm, advanced techniques such as spatial transcriptomics and single-cell RNA sequencing offer novel insights into TAM heterogeneity. Future therapeutic strategies targeting TAMs, including metabolic reprogramming, epigenetic modulators, and immune checkpoint inhibitors, hold promise for improving CRC patient outcomes by shifting the balance toward an anti-tumor immune response.
Validation of WHO 2017 Classification and Identification of Prognostic Factors in Patients with Pancreatic Neuroendocrine Neoplasms: A Real-World Experience in Taiwan.
Ho WP, Chou WC, Hsieh CH … +13 more , Hou MM, Shen WC, Huang PW, Wu CE, Hsu CC, Chang WC, Kuo YC, Hsu HC, Chang CF, Su PJ, Wu RC, Chen JS, Huang WK
J Cancer · 2025 · PMID 41323792 · Full text
Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms with an increasing incidence. This study aims to validate the clinical relevance of the WHO 2017 classification system in the Taiwanese population and identif...
Pancreatic neuroendocrine tumors (PanNETs) are rare neoplasms with an increasing incidence. This study aims to validate the clinical relevance of the WHO 2017 classification system in the Taiwanese population and identify independent prognostic factors for patients with PanNETs. We conducted a retrospective analysis of 176 patients with PanNETs from the Chang Gung Medical Hospital at Linkou in Taiwan, spanning the years 2009 to 2022. Pathology reports were reassessed according to the WHO 2017 classification. Clinical characteristics, treatment patterns, and survival outcomes were documented, with subgroup analyses to compare grade 3 (G3) neuroendocrine tumors and neuroendocrine carcinomas (NEC). The overall 5-year survival rate was 58.7%, with median survival of 107.6 months. Survival rates showed clear stratification across WHO 2017 classifications: G1 (83.1%, median 141.0 months), G2 (55.0%, median 105.2 months), G3 (14.6%, median 21.5 months), and NEC (9.4%, median 19.6 months). Multivariate analysis identified five independent prognostic factors: age over 60 years (HR 1.70), tumor size >2cm (HR 1.893), lymph node involvement (HR 1.801), distant metastasis (HR 3.042), and NEC classification (HR 2.382). NEC demonstrated significantly higher lymph node involvement (81% vs 48%, p=0.026), higher Ki-67 index (69 vs 43.8, p<0.001), and higher rates of metastases compared with G3 NET. Our findings validate the prognostic utility of the WHO 2017 classification, particularly in differentiating NET G3 from NEC. This refined classification system, combined with identified prognostic factors, provides valuable guidance for clinical decision-making and treatment selection in patients with PanNETs.
Comprehensive Bioinformatics Analysis and Validation of the Mechanism of Glutamic-pyruvic Transaminase 2 in Bladder Cancer.
Dong H, Li H, Chen S … +7 more , Wang Q, Zhang Y, Shi H, Zuo J, Chen J, Wang J, Wang H
J Cancer · 2025 · PMID 41323791 · Full text
Glutamic pyruvic transaminase 2 (GPT2) promotes the initiation and progression of various cancers. However, its regulatory role in bladder cancer (BCa) remains unclear. In this study, we aimed to validate the role of GPT...
Glutamic pyruvic transaminase 2 (GPT2) promotes the initiation and progression of various cancers. However, its regulatory role in bladder cancer (BCa) remains unclear. In this study, we aimed to validate the role of GPT2 in BCa using bioinformatics analysis combined with and experiments. We utilized bioinformatic approaches to download GPT2-related genomic datasets and preliminarily analyzed their expression profile and clinical significance in BCa. Multidimensional predictions regarding the mechanisms by which GPT2 influences BCa progression were generated by integrating diverse bioinformatic analyses. These predictions were further validated through and experiments to confirm GPT2 expression patterns and pro-tumorigenic mechanisms. GPT2 is highly expressed in BCa and is associated with a poor prognosis in patients with BCa. GPT2 has been implicated in tumorigenesis, immune cell infiltration, cell proliferation, epithelial-mesenchymal transition (EMT), and maintenance of stemness. GPT2 knockdown reduced EMT and stemness in BCa cells, suppressed their proliferation, invasion, and migration, and inhibited subcutaneous tumor formation and growth in nude mice. Investigating and elucidating the mechanism of GPT2 in bladder cancer (BCa) provides novel evidence for further understanding the pathogenesis of bladder cancer and developing subsequent therapeutic strategies.
Emerging Roles of PTTG1/Securin in Breast Cancer.
Min L, Feng S, Liu X … +5 more , Zhang Y, Zhao M, Shi H, Liu X, Wang T
J Cancer · 2025 · PMID 41323790 · Full text
Securin is a key regulator of chromosome segregation during mitosis. Dysregulation of securin triggers chromosomal instability (CIN) and aneuploidy, which are hallmarks of many solid tumors, including breast cancer (BC)....
Securin is a key regulator of chromosome segregation during mitosis. Dysregulation of securin triggers chromosomal instability (CIN) and aneuploidy, which are hallmarks of many solid tumors, including breast cancer (BC). Recent studies have revealed securin's multifaceted roles in the progression of BC. Overexpression of securin not only enhances the malignant behaviors of BC cells but also correlates with poor clinical outcomes in patients, suggesting its potential as both a therapeutic target and prognostic biomarker. Although interest in securin is growing, comprehensive reviews on its role in BC are sparse. In this review, we summarize the biological function of securin. We then focus on the expression patterns of securin in BC and related experimental models, and their association with CIN. Subsequently, we discuss the significance of securin as a prognostic marker for BC. Lastly, we explore how securin influences the malignant behaviors of BC cells. This review emphasizes the critical connection between CIN and BC pathobiology mediated by securin and offers insights for future research into securin-related mechanisms and therapeutic strategies.
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