Cancer Research and Treatment最新文献

{"title":"Differential Efficacy of Alpelisib by PIK3CA Mutation Site in Head and Neck Squamous Cell Carcinoma: An Analysis from the KCSG HN 15-16 TRIUMPH Trial.","authors":"Kyoo Hyun Kim, Shinwon Hwang, Min Kyoung Kim, Keon-Uk Park, Tak Yun, Keun-Wook Lee, Joo Hang Kim, Bhumsuk Keam, Byoung Chul Cho, So Yeon Oh, Sang Hee Cho, Sangwoo Kim, Sung-Bae Kim, Min Hee Hong, Hye Ryun Kim","doi":"10.4143/crt.2024.1195","DOIUrl":"10.4143/crt.2024.1195","url":null,"abstract":"<p><strong>Purpose: </strong>The TRIUMPH trial was a biomarker-driven umbrella trial for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). This analysis focuses on the PIK3CAα (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) inhibitor alpelisib (arm 1) in patients with phosphoinositide 3-kinase (PI3K) pathway alterations.</p><p><strong>Materials and methods: </strong>Patients with PI3K pathway altered tumors were enrolled in the alpelisib arm of the TRIUMPH study. We conducted a detailed analysis of the correlation between PI3K pathway mutations and treatment outcomes including disease control rate, overall survival (OS), and progression-free survival (PFS).</p><p><strong>Results: </strong>From October 2017 and August 2020, 203 were enrolled, with 42 treated with alpelisib. Response evaluation was possible for 33 patients. Genomic profiles revealed PIK3CA amplifications in 26.2%, and point mutations in E542K (26.2%), E545K (23.8%), and H1047R (9.5%). Neither PIK3CA amplification nor co-occurring TP53 mutations had a notable influence on alpelisib response or survival outcomes. Although the overall response rates were similar between helical domain mutations (E542, E545) and kinase domain mutation (H1047), patients with H1047 mutation exhibited significantly poorer PFS compared to those with non-H1047 PIK3CA alterations (1.6 vs. 7.3 months, p=0.017). OS in patients with H1047 kinase domain mutation showed a trend toward being shorter compared to others, though this difference did not reach statistical significance.</p><p><strong>Conclusion: </strong>Alpelisib showed differential efficacy based on PI3K pathway alterations in patients with R/M HNSCC and was well-tolerated. These findings suggest the usefulness of next-generation sequencing testing-based decision-making when using the targeted agents in R/M HNSCC. We need to confirm results in larger cohorts.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":"968-980"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Value of POST-Treatment Extent of Tumor (POSTTEXT) System in Patients with Hepatoblastoma.","authors":"Hana Jeong, Hee Mang Yoon, Pyeong Hwa Kim, Ah Young Jung, Young Ah Cho, Jin Seong Lee, Kyung-Nam Koh, Jung-Man Namgoong","doi":"10.4143/crt.2024.600","DOIUrl":"10.4143/crt.2024.600","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to assess prognostic values of the POST-Treatment Extent of tumor (POSTTEXT) system and clinical factors after neoadjuvant chemotherapy in hepatoblastoma patients and evaluate benefits of post-treatment imaging and clinical factors concomitant with Children's Hepatic Tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system.</p><p><strong>Materials and methods: </strong>This single-center retrospective study of hepatoblastoma cases (2006-2022) included pediatric patients receiving ≥ 4 cycles of neoadjuvant chemotherapy, with pre- and post-treatment imaging and complete medical records. Clinical data included age, sex, and serum α-fetoprotein (AFP) levels. Cox regression analyses identified predictors of event-free survival (EFS). Time-dependent receiver operating characteristic curves assessed the predictive power of combining the CHIC-HS risk stratification with post-treatment factors. Inter-reader agreement was analyzed using weighted kappa.</p><p><strong>Results: </strong>Among the 109 hepatoblastoma patients, 73 (mean age, 2.2±2.7 years) met the inclusion criteria. Prognostic factors for EFS included AFP levels after the fourth cycle of neoadjuvant chemotherapy (hazard ratio [HR], 1.233; 95% confidence interval [CI], 1.086 to 1.400; p=0.001), tumor size change ratio (HR, 0.654; 95% CI, 0.448 to 0.955; p=0.030), and POSTTEXT annotation factor M (HR, 5.209; 95% CI, 1.639 to 16.553; p=0.005). Incorporating AFP levels after the fourth cycle of neoadjuvant chemotherapy into the CHIC-HS improved predictive power (p=0.043). POSTTEXT system showed better inter-reader agreement than PRE-Treatment Extent of tumor (PRETEXT).</p><p><strong>Conclusion: </strong>Predictors of EFS in hepatoblastoma include AFP levels after the fourth cycle of neoadjuvant chemotherapy, tumor size change ratio, and metastasis (POSTTEXT M). Combining AFP levels after the fourth cycle of neoadjuvant chemotherapy to the CHIC-HS improved the predictive ability.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":"1198-1206"},"PeriodicalIF":3.8,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12527615/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143025228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IFITM1 Influences Natural Killer Cell-Mediated Cytotoxicity by Modulation of HLA class I Expression in Triple-Negative Breast Cancer Cells.","authors":"Heejin Lee, Chanyeon Park, Keunsoo Kang, Soon Auck Hong, Gyungmin Cho, Inyoung Cheon, Young-Ho Ahn, Jung-Sook Yoon, Yoon Ho Ko, Hye Sung Won","doi":"10.4143/crt.2025.444","DOIUrl":"https://doi.org/10.4143/crt.2025.444","url":null,"abstract":"<p><strong>Purpose: </strong>Interferon-induced transmembrane protein 1 (IFITM1) is associated with a poor prognosis in triple-negative breast cancer (TNBC); however, the mechanisms by which IFITM1 contributes to oncogenesis in TNBC are unclear.</p><p><strong>Materials and methods: </strong>We established two stable cell lines: IFITM1-overexpressing cell line (MB-231-IFITM1-OE) and IFITM1 knockdown cell line (BT-20-IFITM1-KD). The transcriptional activity of β-catenin and the cytotoxic activity of natural killer (NK) cells were evaluated using the luciferase assay and the lactate dehydrogenase cytotoxicity assay. The expression of IFITM1, β-catenin, and HLA class I was assessed by immunohistochemistry in patients with TNBC.</p><p><strong>Results: </strong>Knockdown of IFITM1 in BT-20 cells reduced cell proliferation and ectopically expressed IFITM1 in MB-231 cells increased cell proliferation. RNA sequencing analysis revealed that IFITM1 expression positively correlated with the Wnt/β-catenin signaling pathway and NK cell-mediated cytotoxicity. MB-231-IFITM1-OE cells showed increased β-catenin transcriptional activity and NK cell cytotoxic activity compared with controls, while transient knockdown of IFITM1 in MB-231-IFITM1-OE cells led to a decrease in β-catenin transcriptional activity and NK cell cytotoxic activity. MB-231-IFITM1-OE cells exhibited decreased HLA class I expression, which may have contributed to their increased susceptibility to NK cell-mediated lysis. β-catenin or JAK inhibitor reduced NK cell-mediated cytotoxicity via upregulation of HLA class I. Patients with IFITM1 overexpression showed a trend toward increased β-catenin positivity and HLA class I negativity.</p><p><strong>Conclusion: </strong>IFITM1 overexpression was associated with Wnt/β-catenin signaling and NK cell-mediated cytotoxicity via downregulation of HLA class I in TNBC cells, suggesting that IFITM1 might have immunoregulatory effects on the tumor microenvironment.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Vesicle-Derived Adenosine as a Diagnostic Metabolic Biomarker for Pancreatic Ductal Adenocarcinoma.","authors":"Tao Xia, Wenhui Ouyang, Jie Wang, Jinjing Wang, Yiping Mou, Zhengquan Yang, Hezhi Fang, Shanying Gui","doi":"10.4143/crt.2025.510","DOIUrl":"https://doi.org/10.4143/crt.2025.510","url":null,"abstract":"<p><strong>Purpose: </strong>Current non-invasive diagnostic tools for pancreatic ductal adenocarcinoma (PDAC) exhibit limited sensitivity and specificity. This study aimed to identify more accurate plasma biomarkers by profiling extracellular vesicles (EVs), which are enriched in tumor-derived metabolites and proteins.</p><p><strong>Materials and methods: </strong>Plasma samples were collected under strict fasting and standardized processing protocols from patients diagnosed with PDAC, chronic pancreatitis (CP), and tumor-free controls (Ctrl). EVs were isolated from these plasma samples and subjected to comprehensive metabolomic and proteomic profiling to identify disease-specific biomarkers.</p><p><strong>Results: </strong>A biomarker panel comprising adenosine, adenine, and N-acetylneuraminate (AAN) demonstrated outstanding diagnostic performance, achieving an area under the receiver operating characteristic curve (AUC) of 0.968 (95% CI: 0.92-1.00). At a fixed specificity of 96.8%, the panel yielded a sensitivity of 95.0% (95% CI: 85.0%-100.0%), significantly reducing the classification error from 30% with CA19-9 to 5% with the AAN panel. Among individual markers, adenosine alone showed high diagnostic power (AUC=0.952), correlating with increased expression of 5'-nucleotidase ecto (NT5E), indicative of elevated extracellular purine metabolism. Importantly, these features were unique to the EV compartment and outperformed markers derived from total plasma metabolite profiles.</p><p><strong>Conclusion: </strong>The integration of EV metabolomics and proteomics revealed enhanced purine metabolism, particularly elevated extracellular adenosine, as a distinctive hallmark of PDAC. EV-derived adenosine emerges as a highly promising non-invasive biomarker with superior diagnostic accuracy compared to CA19-9.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRRC15 Promotes the Development of Breast Cancer by Regulating Autophagy through the PI3K/AKT/mTOR Signaling Pathway.","authors":"Xinru Fan, Liu Gao, Zheng Zhang, Xu Jiang, Xiawei Wang, Jiayu Shi, Yu Ling, Rundong Yan, Jiani Shi, Li Yu","doi":"10.4143/crt.2025.543","DOIUrl":"https://doi.org/10.4143/crt.2025.543","url":null,"abstract":"<p><strong>Purpose: </strong>Leucine-rich repeats (LRR) play important roles in tumorigenesis and may serve as novel biomarkers for cancer therapy. The expression of leucine-rich repeat-containing protein 15 (LRRC15) is increased in several cancers. However, it is still unknown whether LRRC15 is involved in breast cancer and autophagy.</p><p><strong>Materials and methods: </strong>This study conducted bioinformatic analysis on LRRC15 expression and prognosis in breast cancer. Clinical samples were collected and subjected to immunohistochemistry and qRT-PCR to analyze LRRC15 expression in tissues and serum. Clonal formation, MTT, wound healing, and Transwell assays were used to examined breast cancer cell proliferation, migration, and invasion. Western blotting detected autophagy-related and PI3K/AKT/mTOR signaling pathway proteins.</p><p><strong>Results: </strong>Patients with breast cancer having elevated expression of LRRC15 have a markedly worse prognosis compared with those having lower levels. Furthermore, LRRC15 expression was strongly correlated with tumor aggressiveness and poor differentiation in breast cancer cell lines. Functionally, LRRC15 drives cancer cell proliferation, migration, and invasion. LRRC15 inhibited autophagy in breast cancer cells, thus modulating their proliferative capacity. Mechanistically, LRRC15 exerted these effects by activating the PI3K/AKT/mTOR signaling cascade.</p><p><strong>Conclusion: </strong>LRRC15 regulates autophagy-induced proliferation and other biological activities of breast cancer cells through the PI3K/AKT/mTOR signaling pathway.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alteration of HER2 Status Following Neoadjuvant Chemotherapy in Breast Cancer: A Clinicopathological Analysis Focusing on HER2-Low Status.","authors":"Hyun-Jung Sung, Hyun Jung Kwon, Kyungah Bai, Yul Ri Chung, Hee-Chul Shin, Eun-Kyu Kim, Koung Jin Suh, Se Hyun Kim, Jee Hyun Kim, So Yeon Park","doi":"10.4143/crt.2025.761","DOIUrl":"https://doi.org/10.4143/crt.2025.761","url":null,"abstract":"<p><strong>Purpose: </strong>This study aimed to investigate alteration of HER2 status after neoadjuvant chemotherapy (NAC) in breast cancer and its impact on clinical outcomes of patients, focusing on HER2-low status.</p><p><strong>Materials and methods: </strong>We retrospectively reviewed clinicopathological data of 1,063 breast cancer patients who underwent NAC between 2013 and 2020. Using paired samples of 670 patients with residual disease after NAC, we analyzed HER2 discordance rates between pre- and post-NAC samples, relationships between HER2 discordance and clinicopathological characteristics of tumors, and clinical outcomes of the patients.</p><p><strong>Results: </strong>Pre-NAC HER2-low status was associated with a lower pathological complete response rate and higher Residual Cancer Burden class compared with HER2-zero and HER2-positive status. However, in subgroup analysis by hormone receptor (HR) status, no statistical differences were found in chemo-responsiveness between them. Following NAC, the overall HER2 discordance rate was 21.2% (κ = 0.676), and the most common type of alteration was zero-to-low (11.5%) conversion, followed by low-to-positive (3.6%) conversion. HER2 discordance was significantly associated with lower HER2 levels and HR positivity before NAC, as well as lymphovascular invasion, higher ypT stage, and axillary node metastasis in residual disease after NAC. In survival analyses, HER2 discordance was found to be an independent prognostic factor for poor disease-free survival of the patients, particularly within the HR-positive subgroup.</p><p><strong>Conclusion: </strong>Given the prognostic implications of HER2 discordance which primarily involves zero-to-low conversion and the therapeutic benefits of newly developed antibody-drug conjugates in HER2-low breast cancers, HER2 status should be re-evaluated in surgical resection specimens following NAC.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor-Type-Specific TMB Cutoffs for Improved ICI Outcome Prediction: Large-Scale Analysis with Real-World Targeted NGS Data.","authors":"Ha Ra Jun, Ji-Young Lee, Changseon Lee, Sung-Min Chun","doi":"10.4143/crt.2025.860","DOIUrl":"https://doi.org/10.4143/crt.2025.860","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor mutational burden (TMB) is a potential biomarker for predicting response to immune checkpoint inhibitors (ICIs). However, its clinical utility is limited by methodological inconsistencies. This study aimed to evaluate the predictive value of TMB for ICI outcomes using next-generation sequencing (NGS) data.</p><p><strong>Materials and methods: </strong>We retrospectively analyzed 9,459 patients with cancer who underwent tumor-only targeted NGS. TMB-high (TMB-H) cutoffs were defined using an interquartile range (IQR)-based method and validated by comparing the overall survival (OS) and progression-free survival (PFS) in ICI-treated cohorts against both The Cancer Genome Atlas whole-exome sequencing-derived TMB and the universal 10 mutations per megabase (mut/Mb) cutoff. We also examined programmed cell death-ligand 1 (PD-L1) expression and subclonality to address response heterogeneity.</p><p><strong>Results: </strong>IQR-based TMB-H was significantly associated with longer PFS in the ICI-treated cohort (hazard ratio (HR)=0.85, 95% confidence interval (CI): 0.73-0.98, p=0.02), NGS before ICI subgroup (HR=0.86, p=0.049), and pre-ICI subgroup (HR=0.80, p=0.03). In contrast, the universal 10 mut/Mb cutoff showed no statistical significance. Subgroup analysis revealed significant PFS benefit in bladder (p=0.014), bowel (p=0.013), and uterine cancers (p=0.006). In lung cancer, patients with both TMB-H and very high PD-L1 expression (≥90%) had the longest PFS (HR=0.64, 95% CI: 0.44-0.93, p=0.021). Among the TMB-H samples, high subclonality was associated with worse OS in non-hypermutated cases (p=0.032).</p><p><strong>Conclusion: </strong>Real-world TMB cutoffs derived from distribution-based methods offer improved predictive value for ICI outcomes. Integration of the PD-L1 expression and subclonality status further refines the predictive utility of TMB, improving precision in ICI treatment.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fraction of Cancer Attributable to Occupational Carcinogens in Korea between 2015 and 2030.","authors":"Eun Mi Kim, Dong-Hee Koh, Soseul Sung, Youjin Hong, Sungji Moon, Jung Eun Lee, Kwang-Pil Ko, Sue K Park, Jeehee Min, Sangjun Choi, Ju-Hyun Park, Sang-Gil Lee, Hwan-Cheol Kim, Dong-Uk Park, Inah Kim","doi":"10.4143/crt.2025.193","DOIUrl":"https://doi.org/10.4143/crt.2025.193","url":null,"abstract":"<p><strong>Purpose: </strong>To estimate the contribution of occupational carcinogens to cancer incidence and mortality in the Korean population between 2015 and 2030.</p><p><strong>Materials and methods: </strong>We selected occupational carcinogens classified as International Agency for Research on Cancer (IARC) Group 1 and estimated the prevalence of exposure using data from the Korean CARcinogen EXposure (K-CAREX) and previous studies. Relative risks were calculated using published literature through a meta-analysis. Levin's formula was used to estimate population attributable fraction (PAF) while considering a 15-year latency period between exposure, cancer incidence, and death. Additionally, trends in cancer PAF were calculated up to 2030, assuming constant relative risks and a 15-year latency period.</p><p><strong>Results: </strong>In 2015, the PAFs for occupational carcinogen-related cancer incidence and mortality were 1.00% (men: 1.75%, women: 0.15%) and 1.97% (men: 2.97%, women: 0.33%), respectively, with asbestos being the largest contributor (incidence: 0.48%; mortality: 0.98%). In 2030, the PAFs for occupational carcinogen-related cancer incidence and mortality were 0.34% (men: 0.62%, women: 0.07%) and 0.80% (men: 1.22%; women: 0.15%), respectively, with diesel engine exhaust being projected to become the largest contributor by 2030 (incidence: 0.16%, mortality: 0.41%).</p><p><strong>Conclusion: </strong>The PAFs of occupational carcinogens in Korea between 2015 and 2030 were estimated to be very low in the general population, and the values are expected to decrease over time owing to various regulations to prevent exposure to occupational carcinogens. Therefore, while regulating well-known occupational carcinogens, efforts should be made to monitor newly identified ones to ensure prompt implementation of preventive measures.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LncRNA DGUOK-AS1 Promotes Bladder Cancer Progression by Enhancing EFTUD2 Stability.","authors":"Wenwei Ying, Dingliang Li, Ninghan Feng, Wei Wei","doi":"10.4143/crt.2025.468","DOIUrl":"https://doi.org/10.4143/crt.2025.468","url":null,"abstract":"<p><strong>Purpose: </strong>Long noncoding RNAs (lncRNAs) are increasingly being recognized to play important roles in cancer pathogenesis. However, the functional mechanisms of most lncRNAs remain poorly understood.</p><p><strong>Materials and methods: </strong>RNA sequencing was performed to identify differentially expressed lncRNAs between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). In vitro and in vivo assays were conducted to investigate the functional role of lncRNA deoxyguanosine kinase 1 antisense RNA 1 (DGUOK-AS1). Meanwhile, RNA pull-down, RNA immunoprecipitation, co-immunoprecipitation, Western blot, and reverse transcription quantitative polymerase chain reaction assays were performed to explore the potential regulatory mechanisms of DGUOK-AS1 on its target genes.</p><p><strong>Results: </strong>Our analysis revealed a significant upregulation of lncRNA DGUOK-AS1 in MIBC compared with NMIBC. Functionally, DGUOK-AS1 was found to enhance the proliferation and invasion of bladder cancer (BC) cells by interacting with elongation factor Tu GTP binding domain containing 2 (EFTUD2), a 116-kDa U5 small nuclear ribonucleoprotein component. Mechanistically, DGUOK-AS1 directly binds to EFTUD2 and the deubiquitinating protein valosin-containing protein-interacting protein 1, thereby shielding EFTUD2 from ubiquitination and subsequent degradation. Furthermore, EFTUD2 orchestrates the exclusion of cassette exon 11 from macrophage-stimulating 1 receptor, leading to the production of the RON∆165 isoform. This isoform activates the Akt/PKB signaling pathway, which is crucial for cancer progression.</p><p><strong>Conclusion: </strong>DGUOK-AS1 drives BC progression via the EFTUD2/MST1R/Akt axis, offering a promising therapeutic target for BC treatment.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087939","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effectiveness of CAR-T Cell Therapies for Relapsed/Refractory Follicular Lymphoma: An External Control Arm Study.","authors":"Hee-Jin Seo, Ju Hwan Kim, Sang Eun Yoon, Won Seog Kim, Dong Keon Yon, Ju-Young Shin, Seok Jin Kim","doi":"10.4143/crt.2024.1181","DOIUrl":"https://doi.org/10.4143/crt.2024.1181","url":null,"abstract":"<p><strong>Purpose: </strong>Axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), and lisocabactagene maraleucel (liso-cel) have received regulatory approval for relapsed or refractory follicular lymphoma (r/r FL). However, the data are scare on their comparative effectiveness against the salvage therapies available in real-world settings. This study aimed to indirectly compare treatment outcomes of axi-cel, tisa-cel, and liso-cel versus usual care in South Korean patients with FL.</p><p><strong>Materials and methods: </strong>To assess effectiveness in real-world data, aggregate data from the ZUMA-5, ELARA, and TRANSCEND FL studies were compared with individual patient data from the Samsung Medical Center - Lymphoma Cohort Study (SMC-LCS). Patients meeting ZUMA-5, ELARA, and TRANSCEND FL eligibility criteria were selected as the external control arm. All eligible treatment lines per patient were analyzed as independent episodes and weighted using the matching-adjusted indirect comparison (MAIC) method. Time-to-event outcomes were assessed with weighted Kaplan-Meier analysis, and adjusted hazard ratios (aHR) were estimated using Cox proportional hazards models.</p><p><strong>Results: </strong>Axi-cel included 127 patients, tisa-cel included 94, liso-cel included 101, and 121 episodes from 49 patients were analyzed in the external control arm. The weighted hazard ratios for overall survival (OS) and progression-free survival (PFS) for axi-cel versus the external control were 0.37 (95% CI, 0.21-0.64), 0.35 (95% CI, 0.20-0.59), respectively. For tisa-cel, the HRs were 0.24 (95% CI, 0.11-0.53), and 0.35 (95% CI, 0.20-0.60), respectively. For liso-cel, the HRs were 0.38 (95% CI, 0.13-1.04), and 0.36 (95% CI, 0.15-0.88), respectively.</p><p><strong>Conclusion: </strong>All three CAR-T therapies showed outstanding effectiveness compared to conventional treatments in usual care in South Korea.</p>","PeriodicalId":49094,"journal":{"name":"Cancer Research and Treatment","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}