Anticancer research最新文献

{"title":"Treatment Outcomes After Progression With Enfortumab Vedotin in Patients With Advanced Urothelial Carcinoma.","authors":"Nobuki Furubayashi, Manabu Mochida, Atsuhiro Kijima, Yushi Fujimoto, Motonobu Nakamura, Takahito Negishi","doi":"10.21873/anticanres.17592","DOIUrl":"https://doi.org/10.21873/anticanres.17592","url":null,"abstract":"<p><strong>Background/aim: </strong>Enfortumab vedotin (EV) has been approved for the treatment of advanced urothelial carcinoma (UC) following platinum-based chemotherapy and immune checkpoint inhibitors (ICIs). However, there is no established treatment for patients whose disease progresses while on EV, and the clinical outcomes post-EV treatment are unclear.</p><p><strong>Patients and methods: </strong>From December 2021 to January 2025, 33 patients with advanced UC received EV monotherapy. After excluding those who discontinued EV due to adverse events or continued treatment without progression, 18 patients were retrospectively analyzed.</p><p><strong>Results: </strong>The median follow-up was 4.1 months, and 16 patients (88.9%) died at the last follow-up. Ten patients received post-EV treatment (five received chemotherapy and five received ICIs), and eight opted for best supportive care (BSC). The overall survival (OS) was not significantly different between the post-EV and BSC groups (4.6 <i>vs.</i> 3.7 months, <i>p</i>=0.425). No significant differences in the progression-free survival (2.5 <i>vs.</i> 3.2 months, <i>p</i>=0.945) or OS (2.6 <i>vs.</i> 5.1 months, <i>p</i>=0.832) were observed between chemotherapy and ICI treatment in the post-EV treatment group. Patients with lymph node-only metastases had significantly longer OS than those with other metastases (13.5 <i>vs.</i> 3.3 months, <i>p</i>=0.039) in the post-EV treatment group.</p><p><strong>Conclusion: </strong>Post-EV treatment did not significantly improve the survival compared with BSC in patients with advanced UC. However, patients with lymph node-only metastases may show better outcomes than others. Further research is required to identify effective treatment strategies for this population.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2185-2193"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143969231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Light Bladder Net: Non-invasive Bladder Cancer Prediction by Weighted Deep Learning Approaches and Graphical Data Transformation.","authors":"Chi-Hua Tung, Shih-Huan Lin, Kai-Po Chang, Ya-Wen Xu, Min-Ling Chuang, Yen-Wei Chu","doi":"10.21873/anticanres.17572","DOIUrl":"10.21873/anticanres.17572","url":null,"abstract":"<p><strong>Background/aim: </strong>Bladder cancer (BCa) is associated with high recurrence rates, emphasizing the importance of early and accurate detection. This study aimed to develop a lightweight and fast deep learning model, Light-Bladder-Net (LBN), for non-invasive BCa detection using conventional urine data.</p><p><strong>Materials and methods: </strong>We improved LBN's generalization by applying data transformations, adding uniform noise, and employing feature selection methods (mRMR, PCA, SVD, t-SNE) to extract key vectors from its fully connected layer. These vectors were integrated into the original dataset, and multiple machine learning models were trained to enhance classification accuracy. Lastly, weighted voting was used to assign importance across these models.</p><p><strong>Results: </strong>Our approach achieved an accuracy of 0.83, a sensitivity of 0.85, a specificity of 0.80, and a precision of 0.81, indicating robust performance in detecting BCa from urine data.</p><p><strong>Conclusion: </strong>This non-invasive diagnostic method offers rapid, cost-effective predictions. A free online tool is available for clinicians and patients to conveniently detect BCa using standard urine samples at http://merlin.nchu.edu.tw/LBN/.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1953-1964"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Prognostic Factors of Surgical Resection for Pulmonary Metastases From Ovarian Cancer.","authors":"Y O Tsukamoto, Takashi Ohtsuka, Yoshikane Yamauchi, Mingyon Mun, Haruhisa Matsuguma, Hiroshi Hashimoto, Hiroki Fukuda, Ichiro Yosihno, Yasushi Shintani, Masafumi Kawamura","doi":"10.21873/anticanres.17581","DOIUrl":"https://doi.org/10.21873/anticanres.17581","url":null,"abstract":"<p><strong>Background/aim: </strong>Pulmonary metastases (PMs) from ovarian cancer are rare, and the efficacy of surgical intervention is unclear. This study aimed to validate the efficacy of surgical intervention for pulmonary metastases from ovarian cancer.</p><p><strong>Patients and methods: </strong>Cases were taken from the database of the Metastatic Lung Tumor Study Group of Japan from 1996 to 2021, which prospectively registers surgical cases of pulmonary metastases at participating centers. Only patients who underwent radical surgery for pulmonary metastases from ovarian cancer were included. Factors associated with overall survival (OS) were analyzed.</p><p><strong>Results: </strong>The analysis included 48 patients with a mean age of 53.2 years old. The 5-year overall survival rate was 69.9% [95% confidence interval (CI)=51.9%-82.2%], with a median survival period of 121 months (95% CI=64-134 months). Predictors of poorer OS included preoperative extrapulmonary metastasis [hazard ratio (HR)=5.354, 95% CI=1.248-22.97; <i>p</i>=0.024], elevated preoperative tumor marker levels (HR=2.999, 95% CI=1.028-8.705; <i>p</i>=0.044), and a disease-free interval of less than 24 months (HR=4.355, 95% CI=1.004-18.89; <i>p</i>=0.049). On multivariable analysis, preoperative extrapulmonary metastasis remained an independent prognostic factor (HR=6.229, 95% CI=1.216-31.92; <i>p</i>=0.028).</p><p><strong>Conclusion: </strong>This report includes the largest number of patients who underwent resection of PMs from OC. Preoperative extrapulmonary metastasis was identified as an adverse prognostic factor, emphasizing the need for careful consideration of surgical indications. Our results significantly contribute to understanding the prognosis and prognostic factors associated with surgical intervention for PMs from OC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2071-2078"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of Stromal CD25+/CD8+ Lymphocyte Ratio in Patients With Grade 2-3 Cervical Intraepithelial Neoplasia (CIN 2-3): A Retrospective Single-center Study.","authors":"Enrico Simonetti, Sabina Pistolesi, Amerigo Ferrari, Matteo Della Rosa, Federica Mei, Federico DI Cocco, Fabio Taponeco, Stefania Cosio, Alessandro Bonuccelli, Angiolo Gadducci, Tommaso Simoncini, Pietro Bottone, Antonio Giuseppe Naccarato, Lavinia Domenici","doi":"10.21873/anticanres.17578","DOIUrl":"https://doi.org/10.21873/anticanres.17578","url":null,"abstract":"<p><strong>Background/aim: </strong>This study aimed to assess the role of the stromal CD25+/CD8+ (Cluster of Differentiation) lymphocyte ratio and other immunohistochemical markers in predicting the risk of recurrence and human papillomavirus (HPV) persistence after Loop Electrosurgical Excision Procedure (LEEP) conization in patients with grade 2-3 cervical intraepithelial neoplasia (CIN2-3).</p><p><strong>Patients and methods: </strong>A retrospective analysis was conducted on 72 patients who underwent LEEP for CIN2-3 in our Department. Criteria for enrollment included HPV genotyping before and after surgery and a follow-up time ≥18 months. Immunohistochemical analysis assessed CD8+ cytotoxic T cells and CD25+ regulatory T cells in the cervical stroma, and the CD25+/CD8+ ratio was computed. Recurrence of CIN2-3 and HPV persistence after LEEP were the endpoints of the study.</p><p><strong>Results: </strong>CIN2-3 recurrence occurred in 13.9% of patients with smoking, HPV-16/18 infection, positive surgical margins, and CIN3 histology being significant risk factors. A CD25+/CD8+ ratio >1.25 was associated with a shorter disease-free survival (DFS) (<i>p</i>=0.033) and HPV persistence at 18 months (<i>p</i>=0.017) after LEEP at univariate analysis. Adjuvant HPV vaccination reduced the recurrence risk (<i>p</i>=0.004). A lympho-monocyte infiltrate consisting of at least 10% CD25+ T cells was significantly associated with HPV persistence at 18 months (<i>p</i>=0.0046).</p><p><strong>Conclusion: </strong>The CD25+/CD8+ ratio is a promising biomarker for identifying patients at higher risk of CIN2-3 recurrence and HPV persistence post-LEEP. These findings highlight the role of immune profiling in the management of patients affected by CIN2-3 and support the integration of vaccination and personalized follow-up strategies.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2041-2050"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143973142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigallocatechin Gallate Induces <i>miR-192/215</i> Suppression of <i>EGR1</i> in Gastric Cancer.","authors":"Nan Zhou, Yuan Yuan, Huijuan Lin, Jian Wang, Huan Lin, Hassan Ashktorab, Duane Smoot, Zhe Jin, Shutong Zhuang, Ying Qin","doi":"10.21873/anticanres.17571","DOIUrl":"https://doi.org/10.21873/anticanres.17571","url":null,"abstract":"<p><strong>Background/aim: </strong>Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) are key regulators of tumorigenesis. This study investigated the role of the <i>miR-192/215</i>-early growth response protein 1 (EGR1) axis in GC and explored its therapeutic implications.</p><p><strong>Materials and methods: </strong>Combinatorial molecular approaches including dual-luciferase reporter assays and western blot analyses were employed to authenticate <i>EGR1</i> as a direct target of <i>miR-192/215</i>. Multi-modal data analysis incorporating The Cancer Genome Atlas datasets and our institutional cohort (n=56) was conducted to delineate <i>EGR1</i> expression profiles across clinicopathological GC stages. Pharmacological modulation studies were implemented to characterize the dose- and time-dependent effects of epigallocatechin-3-gallate (EGCG) on the <i>miR-192/215-EGR1</i> axis.</p><p><strong>Results: </strong><i>EGR1</i> is a direct target of <i>miR-192/215</i>, with its expression negatively regulated by these miRNAs. Clinical analysis revealed significantly reduced <i>EGR1</i> expression in tumors of early-stage GC (stage I) and cases with superficial invasion depth (T1) (<i>p</i><0.05), suggesting a tumor-promoting role in the early stages of the disease. Higher <i>EGR1</i> levels were associated with poorer overall survival, highlighting its potential as a prognostic biomarker (<i>p</i><0.05). Furthermore, treatment of cells with EGCG transiently up-regulated <i>miR-192/215</i> and down-regulated <i>EGR1</i>, highlighting its therapeutic potential.</p><p><strong>Conclusion: </strong>This study highlights the <i>miR-192/215-EGR1</i> axis as a critical regulator of GC progression and a promising therapeutic target. EGCG may serve as an adjunct therapy for GC. Future studies should focus on the regulatory mechanisms of <i>EGR1</i>, its interaction with the tumor microenvironment, and clinical validation of EGCG and other agents targeting this axis.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1935-1951"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143967237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Appendectomy Mitigates Ulcerative Colitis Activity and Delays Colorectal Cancer Onset: A Retrospective Cohort Study.","authors":"Yusuke Izutani, Takayuki Ogino, Makoto Fujii, Yuki Sekido, Norikatsu Miyoshi, Mamoru Uemura, Tsunekazu Mizushima, Hiroaki Ito, Yuichiro Doki, Hidetoshi Eguchi","doi":"10.21873/anticanres.17594","DOIUrl":"https://doi.org/10.21873/anticanres.17594","url":null,"abstract":"<p><strong>Background/aim: </strong>Ulcerative colitis (UC) is an idiopathic inflammatory disease with rising global incidence, influenced by genetic, environmental, and immunological factors whose interactions remain unclear. Although the appendix appears to influence UC onset and disease activity, few studies have investigated how the timing of appendectomy affects disease activity and colorectal cancer risk. This study aimed to clarify the impact of appendectomy on disease activity and colorectal cancer risk in patients with UC.</p><p><strong>Patients and methods: </strong>We retrospectively analyzed 368 patients with UC treated at Osaka University Hospital and Kinshukai Infusion Clinic between April 2008 and December 2023. Participants were divided into two groups, namely the appendectomy (n=18) and non-appendectomy groups (n=350). We compared background characteristics, clinicopathological factors, and disease course, including Partial Mayo scores, relapse rates, proximal disease extension, medication use, and colorectal cancer development.</p><p><strong>Results: </strong>The appendectomy group showed significantly lower Partial Mayo scores at the most severe flare (4.5 <i>vs.</i> 8; <i>p</i><0.001), fewer relapses (<i>p</i>=0.016), lesser proximal disease extension (<i>p</i>=0.049), and lower use of steroids (<i>p</i>=0.032) and biologics or small molecules (<i>p</i>=0.006). Although colorectal cancer incidence was similar in the groups, the appendectomy group had a significantly longer duration from UC diagnosis to cancer diagnosis (29.3±16.0 <i>vs.</i> 16.0±9.9 years; <i>p</i>=0.033). Patients who underwent appendectomy after UC diagnosis exhibited milder disease activity, while those who underwent appendectomy before diagnosis were older at UC onset (<i>p</i>=0.004).</p><p><strong>Conclusion: </strong>Appendectomy is associated with milder UC activity and may delay disease onset. These findings offer insights into UC pathogenesis and suggest potential preventive approaches.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"2205-2214"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143960164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High Expression of OR1F1 Protein as a Potential Prognostic Biomarker for Esophageal Squamous Cell Carcinoma.","authors":"Shunsuke Yamagishi, Mitsuro Kanda, Takahiro Shinozuka, Yusuke Sato, Dai Shimizu, Chie Tanaka, Shinichi Umeda, Haruyoshi Tanaka, Hideki Takami, Norifumi Hattori, Masamichi Hayashi, Goro Nakayama, Yasuhiro Kodera, Yukiyasu Okamura","doi":"10.21873/anticanres.17575","DOIUrl":"https://doi.org/10.21873/anticanres.17575","url":null,"abstract":"<p><strong>Background/aim: </strong>In patients with esophageal squamous cell carcinoma (ESCC), the identification of biomarkers that enable precise stratification of postoperative prognostic risk is crucial for developing personalized treatment strategies. Biomarker reproducibility across multiple independent cohorts is a key consideration in biomarker discovery.</p><p><strong>Materials and methods: </strong>Transcriptome analysis was performed on primary tumor tissues from patients with ESCC who experienced recurrence in distant organs, thus identifying olfactory receptor family 1 subfamily F member 1 (OR1F1) as a candidate biomarker. OR1F1 protein expression and prognostic value were analyzed in two independent cohorts of patients with ESCC who underwent curative esophagectomy using immunohistochemical staining.</p><p><strong>Results: </strong>In Cohort 1, high expression of OR1F1 protein in ESCC tissues was significantly correlated with reduced overall survival (OS) and disease-free survival (DFS). Multivariate analysis of OS after surgery identified high OR1F1 protein expression as an independent adverse prognostic factor. Likewise, high OR1F1 protein expression in tissues was strongly associated with reduced OS and DFS in Cohort 2. In both cohorts, patient prognosis could be stratified into three distinct risk levels based on the expression level of OR1F1 protein.</p><p><strong>Conclusion: </strong>Tissue OR1F1 protein expression could serve as a valuable prognostic biomarker for patients with ESCC.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1997-2009"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143961503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential Role of PTEN and AKT/PKB Proteins in the Pathogenesis of Ovarian Mature Teratomas.","authors":"Jarosław Bal, Lukasz Fulawka, Marian Gabryś, Marek Murawski, Agnieszka Halon","doi":"10.21873/anticanres.17563","DOIUrl":"https://doi.org/10.21873/anticanres.17563","url":null,"abstract":"<p><strong>Background/aim: </strong>Mature teratomas constitute over 95% of ovarian teratomas and account for more than 44% of all ovarian tumors and over 58% of benign ovarian lesions. The pathogenesis of these tumors is hypothesized to involve disruptions in primary germ cell development, with the PI3K/AKT signaling pathway potentially playing a crucial role. This study aimed to analyze the importance of the PTEN protein and its associated signalling pathway, particularly in relation to AKT kinase activation, in the pathogenesis of mature ovarian teratomas.</p><p><strong>Materials and methods: </strong>Surgical specimens from 117 patients with mature ovarian teratomas and control tissues from contralateral ovaries were analyzed. Immunohistochemical analysis was conducted to evaluate the expression of PTEN and phosphorylated AKT (P-AKT/PKB), a key component of the PI3K/AKT pathway regulated by PTEN. Expression levels were assessed using the semi-quantitative Remmele Immunoreactive Score (IRS).</p><p><strong>Results: </strong>An inverse pattern was observed in PTEN expression, with a higher overall IRS score in the study group despite a lower proportion of PTEN-positive cells. The expression of P-AKT protein was elevated in the studied group, both in terms of IRS score and the percentage of P-AKT reactive cells.</p><p><strong>Conclusion: </strong>The study supports a potential role of the PI3K/AKT pathway in the pathogenesis of mature ovarian teratomas, as evidenced by increased P-AKT expression. The role of PTEN, however, remains unclear due to contradictory findings. Further research with larger control groups is warranted to clarify these observations.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1843-1851"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144061967","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitin-proteasome Pathway-linked Gene Signatures as Prognostic Indicators in Prostate Cancer.","authors":"Yasuo Takashima, Kengo Yoshii, Masami Tanaka, Kei Tashiro","doi":"10.21873/anticanres.17562","DOIUrl":"https://doi.org/10.21873/anticanres.17562","url":null,"abstract":"<p><strong>Background/aim: </strong>Prostate cancer (PCa) is the most frequently diagnosed cancer in men and a leading cause of cancer-related death. While prostate-specific antigen is a widely used biomarker, its specificity is limited. This study investigated the prognostic significance of gene subsets associated with the ubiquitin-proteasome pathway in PCa.</p><p><strong>Materials and methods: </strong>We analyzed transcriptomic and clinical data of 94 early-onset (age <55) patients with prostate cancer using public dataset. Differentially expressed genes linked to the ubiquitin-proteasome system were identified across cancer progression stages. Kaplan-Meier survival analysis, Cox regression, and least absolute shrinkage and selection operator (LASSO) modeling were applied to assess their prognostic potential.</p><p><strong>Results: </strong>Differential expression of <i>IKBKB, UBQLN3, TMUB2, UBE2S</i>, and <i>BRCA1</i> was observed at relative-early stages of pT3a and Gleason 3+4. Similarly, <i>HERPUD1, CDC20, UHRF1, PSMD7, PIAS3, MALT1, TNF, UBD, CD3E, CD247, SOCS1, UBE2C, CARD16, ZAP70, UBA7</i>, and <i>UBE3C</i> expression levels also changed at pT3b and Gleason 4+3. At metastatic stages (pT4 and Gleason ≥8) <i>OASL</i> expression was up-regulated, whereas that of <i>DDB1, RPN1, UBE3B, UBE2H, PPIL2, WWP2</i>, and <i>CDH1</i> was down-regulated. In addition, higher expression of <i>PSMD2, CDC20, NFKB1</i>, and <i>STIP1</i> or lower expression of <i>HERPUD2, NEDD4, ANAPC16, LNX1</i>, and <i>HERPUD1</i> was associated with poor prognoses according to the Kaplan-Meier or receiver operating characteristic analyses for biochemical recurrence-free survival. A LASSO-Cox model identified six gene candidates including <i>LNX1, PSMD2, SUMO4, UBE2C, UBR5</i>, and <i>UHRF1</i>.</p><p><strong>Conclusion: </strong>The identified gene subset provides novel prognostic insights into PCa progression and survival. These findings highlight potential biomarkers and therapeutic targets within the ubiquitin-proteasome pathway, offering new avenues for personalized treatment strategies.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1825-1841"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Acquired Resistance in Alpelisib-treated Gastric Cancer Cells With <i>PIK3CA</i> Mutations and Overcoming Strategies.","authors":"Minsu Kang, Kui-Jin Kim, Ji Hea Sung, Milang Nam, Sung-Hyun Hwang, Woochan Park, Jeongmin Seo, Eun Hee Jung, Koung Jin Suh, Ji-Won Kim, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Jee Hyun Kim, Keun-Wook Lee","doi":"10.21873/anticanres.17567","DOIUrl":"https://doi.org/10.21873/anticanres.17567","url":null,"abstract":"<p><strong>Background/aim: </strong>Alpelisib has shown promise in preclinical studies for treating <i>PIK3CA</i>-mutant gastric cancer (GC), and its combination with chemotherapy has progressed to clinical trials. However, acquired resistance to alpelisib remains a significant challenge. This study aimed to elucidate the mechanisms underlying acquired alpelisib resistance and propose potential therapeutic strategies to overcome it.</p><p><strong>Materials and methods: </strong>Acquired alpelisib-resistant GC cell lines were developed by prolonged drug exposure. Mechanistic studies included whole-exome sequencing, western blotting, immunoprecipitation, Cdc42 and Rac1 activity assays, caspase-3/7 assays, colony formation assays, and sphere formation assays to investigate resistance pathways and therapeutic interventions.</p><p><strong>Results: </strong>Two GC cell lines with acquired resistance to alpelisib, SNU601-R and AGS-R, were successfully developed from SNU601 and AGS. Both acquired alpelisib-resistant cell lines exhibited <i>PTEN</i> functional loss, leading to activation of SRC, STAT1, AKT, and PRAS40 signaling pathways. Combination treatments with pan-PI3K inhibitors or AKT inhibitors successfully overcame resistance. Among these, the combination of capivasertib, an AKT inhibitor, with SN38 demonstrated superior cytotoxic effects. Furthermore, the combination of capivasertib and SN38 significantly reduced the colony forming ability and sphere formation compared to each treatment alone in SNU601-R and AGS-R cells.</p><p><strong>Conclusion: </strong>In alpelisib-treated GC cells with <i>PIK3CA</i> mutations, <i>PTEN</i> functional loss and changes in the associated signaling pathway were identified as important mechanisms of acquired alpelisib resistance. The combination of capivasertib and SN38 effectively overcomes acquired resistance to alpelisib in <i>PIK3CA</i>-mutant GC, providing a preclinical rationale for future clinical trials targeting acquired alpelisib-resistant GC with <i>PIK3CA</i> mutations.</p>","PeriodicalId":8072,"journal":{"name":"Anticancer research","volume":"45 5","pages":"1877-1896"},"PeriodicalIF":1.6,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}