J Cancer [JOURNAL]
Sun
200 papers
Isoliquiritigenin inhibits colorectal cancer progression by targeting the FGFR4/FASN mediated lipid metabolism pathway.
Zhai X, Yang H, Tan Z … +4 more , Wu S, Bao Q, Liang J, Tang H
J Cancer · 2025 · PMID 41210688 · Full text
Colorectal cancer (CRC) is one of the most common malignant tumors. Isoliquiritigenin (ISL), a natural chalcone compound extracted from the roots of licorice and other plants, has demonstrated significant anti-tumor acti...
Colorectal cancer (CRC) is one of the most common malignant tumors. Isoliquiritigenin (ISL), a natural chalcone compound extracted from the roots of licorice and other plants, has demonstrated significant anti-tumor activity in various cancers. However, its specific mechanisms of action against CRC remain unclear. In this study, we investigated the molecular mechanisms underlying the effects of ISL targeting Fibroblast Growth Factor Receptor 4 (FGFR4) in CRC. Our findings revealed that FGFR4 is highly expressed in CRC cell lines, and functional assays demonstrated that silencing FGFR4 significantly inhibits cellular proliferation and migration. Further mechanistic studies showed that FGFR4 regulates fatty acid biosynthesis and the PI3K/Akt signaling pathway, as evidenced by the downregulation of Fatty Acid Synthase (FASN) and PI3K/Akt pathway proteins upon FGFR4 knockdown. Moreover, ISL significantly suppresses CRC cell proliferation and migration while disrupting tumor cell fatty acid metabolism. This study suggests that ISL may inhibit CRC progression by downregulating FGFR4 and suppressing PI3K/Akt-mediated fatty acid metabolism reprogramming.
Effect of hydrogel-spacer implantation and uneven positioning on rectal dose in intensity-modulated radiotherapy for prostate cancer.
Uno M, Tamaki Y, Nonomura K … +8 more , Yamamori U, Burioka H, Nagano N, Ue A, Sonoyama Y, Yoshida R, Kitajima K, Wada K
J Cancer · 2025 · PMID 41210687 · Full text
Implanting a hydrogel spacer in radiation therapy for prostate cancer is effective in reducing rectal dose. Hydrogel spacer can be unevenly distributed. we often encountered in which the hydrogel spacer was not in place...
Implanting a hydrogel spacer in radiation therapy for prostate cancer is effective in reducing rectal dose. Hydrogel spacer can be unevenly distributed. we often encountered in which the hydrogel spacer was not in place at the prostatic apex. This study had two objectives. The first was to analyze whether the rectal dose could be reduced in patients who underwent hydrogel-spacer implantation at our hospital. The second was to analyze whether the rectal dose could be reduced in cases where the hydrogel spacer was unevenly distributed and not in place at the prostatic apex, as compared with cases without hydrogel-spacer implantation. We retrospectively reviewed the records of patients who underwent intensity-modulated radiation therapy for prostate cancer at our hospital between March 2020 and June 2022. Initially, the rectal dose parameters were compared between patients who underwent hydrogel-spacer implantation and those who did not. Additionally, the same parameters were compared between patients who did not undergo hydrogel-spacer implantation and those who did, but in whom the spacer was not in place at the apex. 45 patients did not undergo hydrogel-spacer implantation and 36 patients did. A comparison of rectal dose parameters between patients with and without hydrogel-spacer implantation showed a reduction in all parameters in those with implantation. The 36 patients with hydrogel-spacer implantation included 16 patients in whom the hydrogel spacer was not in place at the apex. A comparison of rectal dose parameters between the 45 patients without hydrogel-spacer implantation and the 16 patients with the hydrogel spacer not in place at the apex showed a reduction in all parameters in the latter group. Hydrogel-spacer implantation was effective in reducing the rectal dose. The rectal dose could be reduced even in cases with uneven distribution of the spacer, as compared with cases without spacer implantation.
From Herb to Hope: A Systematic Exploration of Medicinal Plants' Role in Cancer Therapy.
Alghamdi SS, Alshkrh R, Mohammed AE … +1 more , Alowais SA
J Cancer · 2025 · PMID 41210686 · Full text
Medicinal plants play a critical role in drug development, serving as a valuable source of bioactive compounds. Cancer, characterized by uncontrolled cell proliferation, presents significant challenges in treatment due t...
Medicinal plants play a critical role in drug development, serving as a valuable source of bioactive compounds. Cancer, characterized by uncontrolled cell proliferation, presents significant challenges in treatment due to its multifaceted nature. This study aims to evaluate the anticancer potentials of selected medicinal plants specifically focusing on and studies that evaluate therapeutic implications for cancer treatment. A systematic review was conducted to assess both in and studies involving selected medicinal plants: , , , , , , , , and The review involved analyzing cancer cell lines, plant parts used, extraction methods, and mechanisms of action reported in the literature. A total of sixty-nine articles were identified that investigated the anticancer properties of the selected plants. Notably, , , and exhibited significant anticancer potential. In contrast, , , , , , and had limited studies available. The predominant mechanism of action identified for the anticancer activity was the induction of apoptosis. The findings indicate that these medicinal herbs possess promising therapeutic potential as anti-cancer agents. However, further research is warranted for , , , , , and to enhance understanding of their anticancer activities and explore their full therapeutic capabilities.
OCT4-mediated upregulation of DUSP6 promotes metastasis in non-small-cell lung cancer.
Su BH, Wang CT, Lu CS … +11 more , Huang TH, Wu TC, Su YC, Wu YC, Yen YT, Tseng YL, Cheng LH, Suk CW, Shiau AL, Chang JM, Wu CL
J Cancer · 2025 · PMID 41210685 · Full text
The roles of cancer stem cells and Octamer-binding transcription factor 4 (OCT4) have been implicated in human tumorigenesis and metastasis. However, the role of OCT4 in the metastasis of non-small-cell lung cancer (NSCL...
The roles of cancer stem cells and Octamer-binding transcription factor 4 (OCT4) have been implicated in human tumorigenesis and metastasis. However, the role of OCT4 in the metastasis of non-small-cell lung cancer (NSCLC) remains undetermined, especially regarding stem cell-related pathways. Previous research has reported that dual-specificity phosphatase 6 (DUSP6), a mitogen-activated protein kinase (MAPK) phosphatase, is associated with cancer cells that display anti-apoptotic, migratory, and drug-resistance phenotypes. However, the regulation of DUSP6 in NSCLC is unclear. This study focused on the role of OCT4 in NSCLC, particularly its interaction with DUSP6. Here, we show a positive correlation between OCT4 and DUSP6 expression in NSCLC cells. Overexpression of OCT4 increased, whereas knockdown of OCT4 reduced DUSP6 expression. Luciferase reporter and chromatin immunoprecipitation (ChIP) assays revealed that OCT4 transactivated DUSP6 expression by directly binding to the DUSP6 promoter, indicating that DUSP6 is a downstream target of OCT4. Furthermore, knockdown of DUSP6 in OCT4-overexpressing A549 human NSCLC cells decreased cell migration and reduced tumor growth and pulmonary metastasis in NOD/SCID mice. In conclusion, our findings highlight the importance of the OCT4-DUSP6 pathway in NSCLC progression. Furthermore, the OCT4-DUSP6 axis is a potential therapeutic target for NSCLC.
Integrative Analysis of GEO Datasets and Mendelian Randomization Reveals a Potential Role ofISOC1 in Renal Cell Carcinoma.
Wang J, Liu Y, Yan Z … +7 more , Lu Q, Jian J, Liu X, Chen Z, Zheng Q, Wan S, Wang L
J Cancer · 2025 · PMID 41210684 · Full text
Renal cell carcinoma (RCC) is a leading malignancy of the urinary system, with clear cell RCC (ccRCC) being the most prevalent subtype. Despite advances in treatment, the prognosis of advanced RCC remains poor, and the m...
Renal cell carcinoma (RCC) is a leading malignancy of the urinary system, with clear cell RCC (ccRCC) being the most prevalent subtype. Despite advances in treatment, the prognosis of advanced RCC remains poor, and the molecular mechanisms underlying its pathogenesis are not fully understood. This study utilized multiple renal cancer cohorts from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). By integrating Mendelian randomization (MR) analyses of expression quantitative trait loci (eQTL) and protein quantitative trait loci (pQTL), we investigated causal associations between candidate genes and RCC. Immune infiltration, drug sensitivity, and survival analyses were performed to further explore functional significance. In vitro experiments validated the biological role ofISOC1 in RCC progression. We focused on ISOC1, a gene previously implicated in other malignancies but not well studied in RCC. Through integrative MR analysis, we identified ISOC1 as a novel RCC-associated gene, with potential tumor-suppressive functions in this specific context. ISOC1 expression was significantly linked to tumor immune infiltration, drug sensitivity, and patient prognosis. Functional assays demonstrated that ISOC1 knockdown promoted RCC cell proliferation, migration, and invasion. ISOC1 plays a critical role in RCC progression and may act as a tumor suppressor. These findings highlight ISOC1 as a potential biomarker for prognosis and a promising target for therapeutic intervention in RCC. Moreover, this study underscores the utility of MR-based integrative analyses in uncovering novel molecular mechanisms and therapeutic targets for cancer.
Development and validation of a nomogram to predict prognosis of patients with combined hepatocellular-cholangiocarcinoma after hepatic resection.
Liu R, Wang S, Du Y … +5 more , Wen T, Xiang L, Xie W, Li D, Li H
J Cancer · 2025 · PMID 41210683 · Full text
Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer characterized by a low incidence but a poor prognosis. The purpose of the study was to develop a clinical prediction mode...
Combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CCA) is a rare primary liver cancer characterized by a low incidence but a poor prognosis. The purpose of the study was to develop a clinical prediction model utilizing non-invasive blood markers to effectively evaluate the prognosis of cHCC-CCA patients following hepatic resection. The retrospective analysis was conducted on 125 patients with cHCC-CCA who underwent hepatic resection between April 2013 and October 2022. All cHCC-CCA patients were randomly assigned to the training group (n = 63) and the validation group (n =62). A nomogram based on patient clinical factors was established using cox regression analysis. Receiver operating characteristic curves (ROCs) were used to assess the predictive performance of the model. Calibration and decision curves were employed to evaluate the model's prediction accuracy and goodness of fit. Multivariate analysis revealed significant associations between lymphatic metastasis, microvascular invasion (MVI), gamma-glutamyl transpeptidase to albumin ratio (GAR), carcinoembryonic antigen (CEA), prothrombin time (PT), alpha-fetoprotein (AFP), hepatitis B virus (HBV), and overall survival. Based on these prognostic factors, a nomogram model was established and validated using the validation set. Calibration curves demonstrated good consistency in the 1-year, 3-year, and 5-year survival rates of patients. Additionally, the ROC analysis indicated the model's strong predictive ability, and the decision curves confirmed its clinical applicability. This study successfully developed a nomogram model for predicting survival outcomes in patients with cHCC-CCA following hepatectomy.
Regulating arachidonic acid metabolism: a novel strategy to prevent colorectal inflammatory cancer transformation.
Ren S, Lu L, Su H … +6 more , Li Z, Li S, Pan J, Liu Y, Ji G, Xu H
J Cancer · 2025 · PMID 41210682 · Full text
Colorectal cancer (CRC) ranks among the leading causes of cancer-related morbidity and mortality worldwide, with colitis-associated colorectal cancer (CAC) driven by inflammatory cancer transformation. Arachidonic acid (...
Colorectal cancer (CRC) ranks among the leading causes of cancer-related morbidity and mortality worldwide, with colitis-associated colorectal cancer (CAC) driven by inflammatory cancer transformation. Arachidonic acid (AA), a key ω-6 polyunsaturated fatty acid, and its metabolites, including prostaglandins (PGs) and leukotrienes (LTs), play pivotal roles in this process by modulating inflammation, immune responses, and the intestinal microenvironment. Notably, a multi-enzyme co-expression nanoplatform integrating lipoxygenase (LOX) and phospholipase A (PLA) has been developed, synergistically inducing immunogenic ferroptosis and upregulating AA expression to enhance CD8 T cell-mediated anti-tumor immunity. Additionally, dual COX-2/soluble epoxide hydrolase (sEH) inhibitors, such as PTUPB, demonstrate enhanced anti-tumor activity and reduced toxicity when combined with cisplatin, offering a promising approach to mitigate gastrointestinal side effects of nonsteroidal anti-inflammatory drugs (NSAIDs). Furthermore, natural products like ginsenoside Rk3 and berberine have been identified to regulate AA metabolism and gut microbiota, alleviating CAC by modulating lipid peroxidation and inflammatory pathways. This review synthesizes these innovative findings, highlighting the role of AA metabolism in maintaining intestinal homeostasis, promoting inflammatory cancer transformation, and serving as a therapeutic target to inhibit CAC progression, thus providing new insights into its prevention and treatment.
Gene Signature Associated with Ferroptosis for Predicting Overall Survival among Ovarian Cancer Patients.
Li Y, Wang Y, Lei H … +9 more , Li KW, Tang J, Xu L, Liu Y, Lu J, Peng Y, Fan L, Li X, He J
J Cancer · 2025 · PMID 41210681 · Full text
Distinct from apoptosis, ferroptosis is intricately associated with intracellular iron ions and oxidative stress, representing a unique form of cell demise. In the treatment of ovarian cancer (OC), it assumes a crucial r...
Distinct from apoptosis, ferroptosis is intricately associated with intracellular iron ions and oxidative stress, representing a unique form of cell demise. In the treatment of ovarian cancer (OC), it assumes a crucial role, as research suggests its association with patient prognosis. This investigation delves into the correlation between genes associated with ferroptosis and the prognosis of OC, providing insights into its pathogenesis. Through the examination of mRNA expression using TCGA, ICGC, and GTEx databases, we identified a set of five pivotal genes (CD44, FTH1, ALOX12, SLC7A11, CRYAB) forming a prognostic model. Their regulation affects various aspects of OC, including the cell cycle, proliferation, invasiveness, immune response, and drug tolerance. To summarize, ferroptosis significantly impacts the prognosis of OC, and the targeting of relevant pathways holds potential for enhancing treatment outcomes, thereby guiding future research and personalized therapeutic strategies.
Extrachromosomal circular DNA of multiple myeloma.
Li F, Long X, Tang S … +2 more , Liu J, Fu Y
J Cancer · 2025 · PMID 41210680 · Full text
Extrachromosomal circular DNA (EccDNA) is widespread in various heterogeneous tumors and closely associated with tumor resistance and progression. Circle-seq and mRNA-seq were done on samples from three multiple myeloma...
Extrachromosomal circular DNA (EccDNA) is widespread in various heterogeneous tumors and closely associated with tumor resistance and progression. Circle-seq and mRNA-seq were done on samples from three multiple myeloma (MM) patients, one when they had a complete response and one when they relapsed. A large number of EccDNA molecules were detected with high heterogeneity among the six samples. Circle-seq combined with mRNA-seq analyses revealed that there is no linear relationship between mRNA expression and EccDNA quantity. Chromosome 19 presented the highest density of differentially expressed EccDNA genes, followed by chromosome 17. Only the T3 sample showed del(17p) by fluorescence hybridization at the time of relapse. Approximately 92% of all upregulated EccDNA genes from chromosome 17 (137) were present in the T3 sample. By integrating Circle-seq and mRNA-seq data, we obtained several potentially functional candidate protein-coding genes and miRNAs from chromosome 17. We further assessed the prognostic value of the three protein-coding genes in the MMRF-COMPASS clinical trial and found that all three genes were poor prognostic indicators for MM. Furthermore, WB, CCK8 and Annexin V-FITC/PI assays revealed that the overexpression of 2',3'-cyclic nucleotide 3' phosphodiesterase (CNP) downregulated the apoptotic pathway and increased bortezomib tolerance in MM cells. We performed a Circle-seq analysis of MM and investigated the heterogeneity of EccDNA. Analysis of data from clinical studies and basic experiments revealed that the gene carried on EccDNA most likely contributed to the increased tolerance of bortezomib in MM with del(17p).
Revisiting IGF2BP1 in Endometrial Cancer: Ethnic-Specific Prognostic Implications and Association with Caspase-3 and pSTAT3.
Ho H, Shih CY, Cheng CY … +2 more , Liang YJ, Chen YL
J Cancer · 2025 · PMID 41210679 · Full text
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has emerged as a key N6-methyladenosine reader protein involved in RNA stability and oncogenesis across various cancers. Previous studies, primarily based on...
Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) has emerged as a key N6-methyladenosine reader protein involved in RNA stability and oncogenesis across various cancers. Previous studies, primarily based on Western cohorts, have associated high IGF2BP1 expression with poor prognosis and aggressive tumor behavior in endometrial cancer (EC). However, the prognostic significance of IGF2BP1 in East Asian populations, including those from Taiwan, remains unclear. This retrospective study analyzed 75 paraffin-embedded EC tissue samples from treatment-naïve Taiwanese patients. Immunohistochemical staining was performed to assess IGF2BP1 expression. Patients were categorized into high- and low-expression groups based on a receiver operating characteristic-derived cutoff score of 10. Kaplan-Meier survival analysis and log-rank tests were used to evaluate survival outcomes. Univariable and multivariable logistic regression analyses were employed to explore associations with clinicopathological features and key biomarkers, including caspase-3 and phosphorylated signal transducer and activator of transcription 3 (pSTAT3). Contrary to prior literature, patients with high IGF2BP1 expression (score >10) exhibited significantly better overall survival compared to the low-expression group (log-rank p = 0.029). The high-expression group-maintained survival probabilities above 85% throughout the 4-year follow-up period, while the low-expression group declined below 40%. Furthermore, high IGF2BP1 expression was positively correlated with caspase-3, a key pro-apoptotic marker, and negatively correlated with pSTAT3, a well-known inflammatory and oncogenic signal transducer. These findings suggest that IGF2BP1 may exert context-dependent biological functions in EC, potentially promoting apoptosis and dampening tumor-promoting inflammation in Taiwanese patients. This study provides novel evidence that high IGF2BP1 expression is associated with improved prognosis in Taiwanese patients with EC. These findings highlight potential ethnic differences in IGF2BP1-mediated tumor biology, suggesting that IGF2BP1 may serve as a favorable prognostic biomarker and therapeutic target. Further mechanistic and population-based studies are warranted to clarify its dualistic role in endometrial tumorigenesis.
Correspondence on "Robotic radical hysterectomy for cervical cancer: current trends and controversies".
Rychlik A, Bedyńska M, Querleu D
J Cancer · 2025 · PMID 41059499 · Full text
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The Role of P53 in Immune Evasion and Therapeutic Strategies in Hematologic Malignancies.
Wen J, Fu L, Zhong H … +1 more , Chen H
J Cancer · 2025 · PMID 41049014 · Full text
P53 is a crucial tumor suppressor gene that plays an essential role in maintaining genomic stability, regulating cell cycle progression, and inducing apoptosis. In hematologic malignancies, P53 mutations are frequently a...
P53 is a crucial tumor suppressor gene that plays an essential role in maintaining genomic stability, regulating cell cycle progression, and inducing apoptosis. In hematologic malignancies, P53 mutations are frequently associated with poor prognosis, treatment resistance, and immune evasion. Recent research has highlighted the impact of P53 dysfunction on tumor immune escape mechanisms, including impaired antigen presentation, altered cytokine signaling, and recruitment of immunosuppressive cells. This review integrates recent findings on P53 mutations in hematologic malignancies, focusing on their role in immune evasion and potential therapeutic strategies aimed at restoring P53 function or targeting associated pathways. Understanding these mechanisms may provide new insights into the development of effective immunotherapeutic approaches for hematologic cancers.
Nomogram for predicting axillary pathologic complete response after neoadjuvant systemic therapy in HER2 positive and triple negative breast cancer.
Shi Z, Zhu H, Bian X … +3 more , Qian X, Meng J, Zhang J
J Cancer · 2025 · PMID 41049013 · Full text
With the continuous improvement in the efficacy of neoadjuvant therapy (NAT), a significant proportion of breast cancer patients initially diagnosed with pathologically confirmed axillary lymph node metastasis (pN+) may...
With the continuous improvement in the efficacy of neoadjuvant therapy (NAT), a significant proportion of breast cancer patients initially diagnosed with pathologically confirmed axillary lymph node metastasis (pN+) may achieve ypN0 status (no residual nodal metastasis) following NAT. This study aims to develop a predictive model for estimating the probability of achieving ypN0 status after NAT, thereby assisting surgeons in making optimal decisions regarding axillary management strategies. This retrospective study enrolled 671 patients diagnosed with pN+ at Tianjin Medical University Cancer Institute and Hospital between December 2018 and December 2022, all of whom completed NAT followed by surgical intervention. The cohort comprised 428 HER2-positive and 243 TNBC patients. Clinicopathological and ultrasound imaging data were systematically collected. Patients were stratified into training and validation sets at a 7:3 ratio based on admission dates. Univariate analysis was initially performed on the training set to identify potential factors associated with achieving ypN0 status post-NAT. Variables demonstrating statistical significance were subsequently incorporated into a multivariate logistic regression analysis to determine independent predictors. A predictive nomogram was then constructed using these independent factors via R software for visual interpretation of ypN0 probability. The predictive performance of the model was ultimately evaluated by generating receiver operating characteristic (ROC) curves to assess discriminative ability and calibration curves to quantify prediction accuracy, with further validation performed using the independent validation cohort. In HER2 positive breast cancer patients, those exhibiting histological grade III, HER2 IHC 3+ expression, absence of lymphovascular invasion, clinical N1 stage, prominent and hypervascular tumor CDFI signal pre-NAT, and achievement of breast pathological complete response (bpCR) following NAT were significantly more likely to achieve ypN0 status. Conversely, among TNBC patients, independent predictors of post-NAT ypN0 achievement included histological grade III, taxane-platinum combination regimens, bpCR, dot-linear signals in axillary lymph nodes on post-NAT ultrasound, and minimal transverse diameter of node on final post-NAT ultrasound evaluation. This study established distinct predictive models for HER2-positive and TNBC cohorts with initial pN+ status to estimate the probability of achieving ypN0 following NAT. Both models demonstrated robust predictive performance through rigorous validation, providing clinicians with quantitative tools to optimize axillary management strategies and facilitate precision-based individualized treatment planning.
Skin Cancer: Epidemiology, Screening and Clinical Features of Acral Lentiginous Melanoma (ALM), Melanoma (MIS), Nodular Melanoma (NM) and Superficial Spreading Melanoma (SSM).
Lu CT, Lin TL, Mukundan A … +4 more , Karmakar R, Chandrasekar A, Chang WY, Wang HC
J Cancer · 2025 · PMID 41049012 · Full text
Melanoma, a highly aggressive form of skin cancer, presents considerable challenges in early detection and accurate diagnosis, particularly across its diverse subtypes such as acral lentiginous melanoma (ALM), melanoma...
Melanoma, a highly aggressive form of skin cancer, presents considerable challenges in early detection and accurate diagnosis, particularly across its diverse subtypes such as acral lentiginous melanoma (ALM), melanoma (MIS), nodular melanoma (NM), and superficial spreading melanoma (SSM). This study assesses the epidemiology, clinical characteristics, and screening techniques related to various melanoma subtypes, emphasizing their distinct features and risk factors. Moreover, the use of machine learning (ML) methodologies to categorize melanoma subtypes and the thorough examination of advancements in AI-based melanoma diagnosis, primarily emphasizing convolutional neural networks (CNN) and transfer learning approaches. Evaluate the efficacy of several deep learning models in classifying melanoma subtypes while addressing significant obstacles, including class imbalance and model generalization. Furthermore, it contemplates the integration of multimodal data, including genetic information and patient demographics, to enhance diagnostic accuracy. This comprehensive review assesses the epidemiology, clinical characteristics, and machine learning techniques utilized for the classification and detection of different melanoma subtypes, emphasizing recent advancements in AI-driven methods and their clinical significance.
SREBP1-SCD1 enhanced MUFAs Biosynthesis drives Nutrient Deprived Pancreatic cancer cell Ferroptosis Resistance.
Zhang Z, Cai X, Gong Y … +4 more , Gong A, Liao X, Gao J, Wang D
J Cancer · 2025 · PMID 41049011 · Full text
As the most disastrous tumor microenvironment of pancreatic cancer, nutrient deprivation determined various cancer cell biology, especially the cell death resistance. Our objective is to elucidate the role of nutrient de...
As the most disastrous tumor microenvironment of pancreatic cancer, nutrient deprivation determined various cancer cell biology, especially the cell death resistance. Our objective is to elucidate the role of nutrient deprivation in ferroptosis resistance of pancreatic cancer cells and to explore potential therapeutic strategies to overcome it. To replicate the nutrient-deprived tumor microenvironment, pancreatic cancer cell lines (PANC1 and Patu8988T) were cultured in Dulbecco's Modified Eagle Medium (DMEM) supplemented with 2% fetal bovine serum (FBS). Ferroptosis was assessed by Cell Counting Kit-8 (CCK8), Malondialdehyde (MDA) assay, and C11 BODIPY staining. The signaling activity was assessed via western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Ferroptosis inducers promoted pancreatic cancer cell death could be significantly reversed under nutrient deprivation condition. Nutrient deprivation upregulated the expression of SREBP1 and SCD1, leading to increased intracellular levels of monounsaturated fatty acids (MUFAs). Genetic knockdown of SREBP1 or SCD1, as well as treatment with rapamycin (an mTOR inhibitor), reversed the nutrient deprivation induced increase in mature SREBP1 and SCD1 expression and restored lipid peroxidation both and . The synergistic application of sorafenib and rapamycin yielded a profoundly efficacious therapeutic outcome . Our findings demonstrate that nutrient-deprived pancreatic cancer cells adaptively enhance MUFA biosynthesis through the SREBP1-SCD1 axis, conferring resistance to ferroptosis. This resistance can be effectively overcome by combination therapy with sorafenib and rapamycin, offering a promising strategy to target the ferroptosis vulnerability shaped by the pancreatic tumor microenvironment.
Phase 1b Study of Tovorafenib, Plozalizumab or Vedolizumab Plus Standard-of-Care Immune Checkpoint Inhibitors in Patients with Advanced Melanoma.
Sullivan RJ, Tsai KK, Pavlick AC … +6 more , Buchbinder EI, Agarwala SS, Ribas A, Jansson J, Rossiter G, Olszanski AJ
J Cancer · 2025 · PMID 41049010 · Full text
Novel advanced melanoma therapy combinations may increase treatment efficacy and reduce treatment-related toxicities. This open-label, nonrandomized, multicenter, phase 1b, 3-arm, umbrella study enrolled patients with a...
Novel advanced melanoma therapy combinations may increase treatment efficacy and reduce treatment-related toxicities. This open-label, nonrandomized, multicenter, phase 1b, 3-arm, umbrella study enrolled patients with advanced melanoma eligible for standard-of-care checkpoint inhibitor therapy. There were 3 phases: dose escalation; Part 1 limited cohort expansion; Part 2 additional expansion. Arms (A) 1, 2, and 3 investigated tovorafenib plus nivolumab, plozalizumab plus nivolumab, and vedolizumab plus nivolumab plus ipilimumab, respectively. In the dose-escalation plus Part 1 limited cohort expansion phase, the primary endpoint was dose-limiting toxicities. Twenty-two patients (A1=1; A2=9; A3=12) were enrolled before premature study termination. A1 was closed due to lack of enrollment. A2 enrollment was closed due to lack of clinical benefit (6/9 patients discontinued due to disease progression), and A3 enrollment was closed due to meeting prespecified stopping criteria (grade 3 diarrhea/colitis in 2 patients). One patient (A2) experienced dose-limiting toxicities. Grade ≥3 adverse events were reported in the single patient from A1, 3 (33.3%) patients from A2, and 10 (83.3%) patients from A3. Study design allowed early termination after initial results suggested unlikely clinical benefit. Efficacy remains inconclusive for tovorafenib plus nivolumab and vedolizumab plus nivolumab plus ipilimumab in advanced melanoma. Trend review in this small population suggests a limited effect of investigated vedolizumab regimens as primary prophylaxis against nivolumab plus ipilimumab gastrointestinal toxicity.
Identification and validation of the PARP inhibitor-related gene KANK3 for predicting prognosis and immunotherapeutic response in prostate cancer.
Zhao Y, Wang Q, Qin X … +8 more , Jiang W, Li H, Xu M, Li X, Ye H, Zhou J, Chen X, Wu G
J Cancer · 2025 · PMID 41049009 · Full text
Prostate cancer (PCa), a prevalent malignant neoplasm in men, has its biochemical recurrence-free survival (BCRFS) serving as a critical determinant for patient prognosis. PARP inhibitors have demonstrated potential ther...
Prostate cancer (PCa), a prevalent malignant neoplasm in men, has its biochemical recurrence-free survival (BCRFS) serving as a critical determinant for patient prognosis. PARP inhibitors have demonstrated potential therapeutic value in the management of PCa. Nevertheless, the precise influence exerted by their associated genes on BCRFS remains elusive. We selected the differentially expressed genes after treatment with olaparib and defined them as PARP inhibitor-related genes (PIRGs). Consensus clustering was employed to evaluate the relationships among different PIRGs clusters, prognosis, and the immune microenvironment. Univariate COX regression analysis was used to screen the prognosis-related PIRGs, which were then incorporated into multiple machine learning frameworks. The random forest algorithm with the highest C-index was chosen to construct a BCRFS prediction model. A prognostic nomogram was developed based on the risk score and clinical information, and the predictive performance of the model was assessed. In C4 - 2B and LNCaP cell lines, 230 and 58 genes were differentially expressed, respectively. Consensus clustering results showed distinct survival prognoses and immune - infiltrated microenvironments among different groups. The random forest model had a high average C - index in both the training and validation sets. The prognostic model constructed in this study demonstrated a higher C-index compared to the prognostic models from previous studies. High - risk group patients had a poor immunotherapy response. A nomogram based on risk scores and clinical information accurately predicted PCa patients' BCRFS. Cell experiments revealed that KANK3 was downregulated in PCa and upregulated by olaparib treatment. KANK3 overexpression in PCa cell lines inhibited cell proliferation, migration, and invasion, suggesting its oncogenic role in PCa. Our study has described the correlations between PARP inhibitor-related genes and the immune landscape, recurrence after radical prostatectomy, as well as clinical characteristics. The risk score can improve the existing risk stratification system.
Epigenetic alterations in triple-negative breast cancer and their clinical implications for diagnosis and therapy.
Go EJ, Oh JH
J Cancer · 2025 · PMID 41049008 · Full text
Breast cancer, including triple-negative breast cancer (TNBC), is the most commonly diagnosed cancer in women, with subtypes differing in treatment options and prognoses. In particular, TNBC, characterized by the absence...
Breast cancer, including triple-negative breast cancer (TNBC), is the most commonly diagnosed cancer in women, with subtypes differing in treatment options and prognoses. In particular, TNBC, characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression, is the most aggressive subtype, with limited treatment options, high metastatic rates, and poor survival outcomes. In recent years, epigenetic studies have emerged as a promising tool for analyzing gene expression and alterations in TNBC, providing potential insights into the development of novel therapeutic strategies. Epigenetic mechanisms, such as DNA methylation, histone modifications, and non-coding RNA (ncRNA)-mediated gene silencing, play a crucial role in the development and progression of TNBC. Research into these mechanisms holds significant promise for the development of personalized therapeutic approaches, potentially improving outcomes for TNBC patients. This review provides a comprehensive overview of recent advances in research on epigenetic alterations in TNBC, with an emphasis on potential clinical applications aimed at improving survival and quality of life in TNBC patients.
Disulfidptosis-Associated CCNB2: A Prognostic Biomarker and Immune Microenvironment Modulator in Prostate Cancer.
Jiang W, Wang Q, Zhou J … +6 more , Zhao Y, Qin X, Li X, Li H, Wang L, Wu G
J Cancer · 2025 · PMID 41049007 · Full text
Disulfidptosis, a newly recognized form of cell death activated by disulfide bond stress, differs from apoptosis, ferroptosis, cuproptosis, and pyroptosis. Understanding its role in prostate cancer is essential for devel...
Disulfidptosis, a newly recognized form of cell death activated by disulfide bond stress, differs from apoptosis, ferroptosis, cuproptosis, and pyroptosis. Understanding its role in prostate cancer is essential for developing tailored therapeutic approaches for managing this condition. Here, we establish the first disulfidptosis-based molecular subtyping framework for prostate cancer (PCa) and identify CCNB2 as a novel regulator of disulfidptosis, revealing its dual role in apoptosis activation and immune microenvironment remodeling. We used consensus clustering to classify disulfidptosis into different subtypes and to study the unique characteristics linked to each one. We also developed a Dis score to measure the severity of each patient's subtype. We compared immune infiltration, pathway enrichment, and survival differences among the subtypes and revealed that the level of the score is significantly associated with the prognosis of PCa.Subsequently, we used Cytoscape software to further filter out hub genes and investigated how these genes influence the progression of PCa and their potential mechanisms through and experiments. We identified three molecular subtypes associated with disulfidptosis (Cluster A, B, C) and three gene subtypes (GeneCluster A, B, C). Each subtype exhibited a distinct prognosis, level of immune cell infiltration, and biological pathway activation. Notably, Cluster B and GeneCluster B, characterized by elevated disulfidptosis gene expression, were correlated with favorable prognosis. Additionally, we discovered that patients with higher scores exhibited lower tumor mutational burden (TMB) and improved prognosis. Finally, our experimental results confirmed that downregulation of CCNB2 expression promoted disulfidptosis in prostate cancer cells, thereby inhibiting their migration and proliferation capacities. This study demonstrates that disulfidptosis can be utilized to stratify risk in patients with PCa. Furthermore, the CCNB2 gene emerges as a potential therapeutic target for prostate cancer by regulating disulfidptosis, thereby influencing the biological behaviors of PCa cells, including their proliferation and migration.
Lipid-Coated Mesoporous Silica Particles for pH-Sensitive Tumor-Targeted Paclitaxel: Development, Characterization.
Deng Y, Zhang T, Zhou J … +10 more , Su Z, Cao Y, Luo J, Zhao L, Hua J, Wang G, Xiao M, Ban J, Zhang Y, Liang H
J Cancer · 2025 · PMID 41049006 · Full text
Nanoparticle carriers can selectively deliver the drug cargo to tumor cells, thus having the ability to prevent early drug release, reduce non-specific cell binding, and prolong drug retention. We constructed paclitaxel...
Nanoparticle carriers can selectively deliver the drug cargo to tumor cells, thus having the ability to prevent early drug release, reduce non-specific cell binding, and prolong drug retention. We constructed paclitaxel (PTX)-loaded lipid-shell mesoporous silica nanoparticles (LMSNs) for targeted anti-cancer drug delivery. The physical properties of PTX-LMSNs were analyzed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The drug loading %) and entrapment efficiency (%) of PTX-LMSNs were measured by high performance liquid chromatography (HPLC). drug release test, imaging, tissue distribution and pharmacokinetics of PTX-LMSNs were also evaluated. The SEM examination showed that MSNs were sphere, whereas TEM showed that they were rich in fine pores. The uniform core-shell structure of PTX-LMSNs was also verified by TEM. The DL capacity of PTX-LMSN was as high as 21.75%, and PTX was released from the nanoparticles in a pH-dependent manner. The cumulative amount of free PTX increased at lower pH, which is conducive to selective drug release from LMSNs in the acidic tumor tissues. imaging showed prolonged retention of PTX-LMSNs, which is beneficial to their therapeutic efficacy. In addition, PTX-LMSNs were primarily concentrated in the liver. Pharmacokinetic experiments showed that the half-life of PTX-LMSNs was 23.21% longer and 79.24% higher than that of Taxol. Together, LMSNs are a highly promising antineoplastic drug carrier system.
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