American journal of cancer research最新文献

{"title":"Targeting ferroptosis and immune surveillance in gastric cancer with traditional Chinese medicine monomers: a dual-targeted strategy for epithelial-mesenchymal transition and angiogenesis.","authors":"Yijia Ma, Lichao Han, Qianyue Ni, Hao Liang, Baojiang Chen, Zijian Wang, Yu Jia, Yimin Xu, Zheng Liu","doi":"10.62347/KSKH3925","DOIUrl":"10.62347/KSKH3925","url":null,"abstract":"<p><p>Gastric cancer (GC) is a highly prevalent and lethal malignancy worldwide. Tumor progression is driven by epithelial-mesenchymal transition (EMT) and aberrant angiogenesis, which collectively facilitate invasion, metastasis, and immune evasion. Ferroptosis, a form of programmed cell death induced by iron-dependent lipid peroxidation, has recently emerged as a promising mechanism to eliminate GC cells, overcome apoptosis resistance, and inhibit migration. Remodeling the tumor immune microenvironment to enhance immune surveillance represents another advanced therapeutic strategy. Natural compounds derived from traditional Chinese medicine (TCM), such as quercetin and curcumin, exert multi-targeted anti-tumor effects by modulating ferroptosis, EMT, angiogenesis, and the immune microenvironment. This review synthesizes evidence from both in vitro and in vivo studies supporting the role of TCM monomers in co-regulating ferroptosis and immune surveillance in GC. Furthermore, it proposes a dual-target approach against EMT and angiogenesis to advance the theoretical framework and promote the clinical application of TCM in precision oncology, thereby guiding the development of novel, low-toxicity, and high-efficacy anti-cancer agents.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3617-3631"},"PeriodicalIF":2.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum: Livin promotes tumor progression through YAP activation in ovarian cancer.","authors":"Jianhua Gao, Wei Han, Yanan He, Jun Zhou, Jintian Miao, Guangmei Zhang","doi":"10.62347/FLCN5855","DOIUrl":"10.62347/FLCN5855","url":null,"abstract":"<p><p>[This corrects the article on p. 3179 in vol. 10, PMID: 33163264.].</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3813-3816"},"PeriodicalIF":2.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432576/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced prognostic stratification in early-stage epithelial ovarian cancer: multi-histological analysis of neutrophil-to-lymphocyte ratio with particular emphasis on clear cell histology.","authors":"En-Ling Sung, Hao Lin, Yu-Che Ou, Hung-Chun Fu, Mei-Yi Lin, Chien-Hsiang Kao, Chen-Hsuan Wu, Chan-Chao Changchien","doi":"10.62347/BETA4769","DOIUrl":"10.62347/BETA4769","url":null,"abstract":"<p><p>In Asian populations, early-stage ovarian cancers account for approximately half of cases, substantially exceeding proportions observed in Western cohorts, with clear cell carcinoma (CCC) and endometrioid carcinoma (EMC) demonstrating markedly higher prevalence in Asian women. The tumor immune microenvironment critically influences oncological progression, and systemic inflammatory biomarkers can serve as surrogates of host immunological responses. This study evaluated the prognostic value of the neutrophil-to-lymphocyte ratio (NLR), an established index of systemic inflammation and immune dysregulation, across histologic subtypes in early-stage epithelial ovarian cancer. We retrospectively analyzed patients with FIGO stage I-II epithelial ovarian cancer diagnosed between 2011 and 2018. Pretreatment NLR was calculated to reflect the balance between neutrophil-driven inflammation and lymphocyte-mediated immunity. Among 217 enrolled patients, CCC (28.1%) and EMC (34.6%) constituted the predominant histotypes, consistent with Asian demographic patterns. In univariable analyses, elevated NLR and advanced stage significantly correlated with diminished progression-free survival (HR 5.04, P<0.001; HR 3.81, P<0.001) and overall survival (HR 4.54, P=0.013; HR 3.91, P=0.003). In multivariable models, NLR remained an independent prognostic factor for both endpoints (PFS: HR 5.38, P=0.001; OS: HR 4.27, P=0.048). Histology-stratified analyses revealed distinctive immunological signatures, with elevated NLR in CCC patients exhibiting exceptionally strong prognostic value (univariable PFS: HR 8.14, P=0.001; OS: HR 22.42, P=0.005; multivariable PFS: HR 8.00, P=0.007; OS: HR 32.43, P=0.025), providing information beyond FIGO stage. Conversely, NLR demonstrated no prognostic relevance in EMC patients, indicating heterogeneous immune microenvironments across histological variants. Elevated pre-treatment NLR independently predicts adverse outcomes in early-stage epithelial ovarian cancer, with particularly pronounced prognostic utility in CCC. These findings may be especially relevant in Asian populations, in which CCC is more common, and could inform personalized risk stratification.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3632-3644"},"PeriodicalIF":2.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analysis of risk factors and development of a risk prediction model for postoperative hypocalcemia in differentiated thyroid cancer.","authors":"Xiaoling Deng, Nengying Zhang, Kaiguo Long, Feng Zeng","doi":"10.62347/KCSV1296","DOIUrl":"10.62347/KCSV1296","url":null,"abstract":"<p><strong>Objective: </strong>To systematically analyze the risk factors of hypocalcemia following surgery for differentiated thyroid cancer (DTC), and to develop and validate a high-precision Nomogram-based prediction model, so as to provide a basis for accurate clinical prevention and management.</p><p><strong>Methods: </strong>This retrospective analysis included 597 DTC patients admitted between March 2019 and January 2025 (training set: n=353; validation set: n=133: external validation set: n=111). Patient features (age, sex, body mass index, diabetes history, etc.), surgical factors (thyroidectomy extent, lymph node dissection, etc.), pathological characteristics (capsular invasion, Tumor, Node, Metastasis [TNM] staging, etc.), and postoperative biochemical indicators (intact parathyroid hormone [iPTH] and blood calcium) were collected. Independent risk factors were screened by univariate and multivariate logistic regression. A Nomogram was constructed based on these factors, and its predictive performance was evaluated using the area under the receiver operating characteristic (ROC) curves (AUC), calibration plots, and decision curve analysis (DCA), with comparisons made to postoperative iPTH-based predictions.</p><p><strong>Results: </strong>Multivariate logistic regression identified the following as independent predictors of hypocalcemia: diabetes history (OR=3.132, P=0.006), bilateral thyroidectomy (OR=2.142, P=0.023), lateral compartment lymph node dissection (OR=2.011, P=0.037), capsular invasion (OR=3.196, P<0.001), surgical time (OR=10.843, P<0.001), and intraoperative bleeding (OR=7.493, P<0.001). The Nomogram model exhibited excellent discriminatory ability across the training (AUC=0.888), validation (AUC=0.866), and external validation sets (AUC=0.913). Calibration curves and DCA demonstrated that the Nomogram had high prediction consistency and clinical net benefits (peak net benefits: 56.94%, 62.40%, and 63.90%, respectively). Moreover, the model significantly outperformed iPTH-based predictions in both the training (P=0.019) and external validation cohorts (P=0.042).</p><p><strong>Conclusions: </strong>Diabetes history, bilateral thyroidectomy, lateral lymph node dissection, capsular invasion, prolonged surgical time (≥82.5 min), and increased intraoperative bleeding (≥25.5 mL) are significant risk factors for postoperative hypocalcemia in DTC patients. The Nomogram model, integrating these factors, outperforms iPTH-based predictions and offers a precise tool for preoperative risk assessment and postoperative management to reduce hypocalcemia and improve patient outcomes.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3645-3660"},"PeriodicalIF":2.9,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432564/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEA and CA 19-9 combined tumor marker index as a prognostic tool for metastatic pancreatic cancer: is two better than one?","authors":"Bilgin Demir, Merve Bıyıklı Alemdar, Onur Yazdan Balçık","doi":"10.62347/JYAD4332","DOIUrl":"10.62347/JYAD4332","url":null,"abstract":"<p><p>Metastatic pancreatic cancer (PC) is one of the cancers with the worst prognosis, and prognostic tests are lacking in this population. If an effective prognostic indicator can be identified, the patient population can be monitored more closely. This retrospective study aimed to investigate the prognostic impact of tumor marker index (TMI) in patients with metastatic PC. Patients diagnosed with metastatic PC at Aydın Adnan Menderes University between 2019 and 2024 were included in the study. Demographic data, tumor marker levels, and treatment received were recorded. The prognostic value of TMI was determined as 3.15 using the receiver operating characteristic (ROC) method. Progression-free survival (PFS) and overall survival (OS) were recorded. 218 metastatic PC patients with a median follow-up duration of 10.81 months were included in the study. The median PFS was 7.26 months for the High TMI group, while it was 10.76 months for the Low TMI group (P=0.003). The median OS of patients with high TMI was 9.3 months, which was significantly lower than the 17.9 months observed in the low TMI group (P<0.001). TMI is a simple and, cost-effective prognostic tool for metastatic PC, and a higher TMI is associated with poorer survival outcomes.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3557-3569"},"PeriodicalIF":2.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432577/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surgical outcomes and prognostic factors of neoadjuvant chemotherapy followed by interval debulking surgery in advanced ovarian cancer.","authors":"Lu Bai, Shuhua Zhao, Jia Xu, Yan Gao, Yuanyuan He, Yanjie Ren, Xiaohong Zhang","doi":"10.62347/LKZC2827","DOIUrl":"10.62347/LKZC2827","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the surgical outcomes and prognostic factors of neoadjuvant chemotherapy (NACT) combined with interval debulking surgery (IDS) in patients with advanced ovarian cancer.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on clinical data of 97 patients with advanced ovarian cancer admitted to Xijing Hospital of The Fourth Military Medical University from January 2018 to December 2019. The patients were divided into two groups based on their treatment methods: a control group (primary debulking surgery (PDS), n=48) and an observation group (NACT combined with IDS, n=49). Short-term efficacy, perioperative outcomes, tumor markers, immune function, quality of life, adverse reactions, and survival status were compared between the two groups. Factors affecting prognosis were analyzed, a Nomogram prediction model was constructed and validated.</p><p><strong>Results: </strong>The observation group demonstrated superior short-term efficacy than the control group, with lower intraoperative blood loss, shorter hospitalization duration, and reduced transfusion volume (<i>P</i><0.05). After treatment, tumor marker levels, immune function, and quality of life improved significantly in both groups compared to pre-treatment levels, with more pronounced improvements in the observation group (<i>P</i><0.05). The incidence of adverse reactions such as liver injury, kidney injury, nausea and vomiting, and myelosuppression was lower in the observation group than in the control group (<i>P</i><0.05). Additionally, no significant difference in 5-year progression-free survival (PFS) and overall survival (OS) was observed between the two groups (<i>P</i>>0.05). Univariate and multivariate regression analyses identified age ≥50 years, tumor size >10 cm, low differentiation, PDS, and presence of residual lesions as independent prognostic factors. The Nomogram prediction model achieved an AUC of 0.955 (95% CI: 0.917-0.993), with calibration curves closely aligning with the ideal line, indicating high predictive accuracy and reliability.</p><p><strong>Conclusion: </strong>NACT combined with IDS demonstrated superior short-term efficacy compared to traditional PDS in patients with advanced ovarian cancer, with improved perioperative conditions, reduced adverse reactions, and enhanced survival rates. Age, tumor size, histological differentiation, and treatment modality independently affect patient prognosis. The Nomogram prediction model developed in this study demonstrates excellent discriminative power and clinical applicability for prognostic evaluation.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3603-3616"},"PeriodicalIF":2.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A high-risk prediction model for endometrial cancer: exploring the synergistic interaction between polycystic ovary syndrome and metabolic syndrome.","authors":"Qian Xu, Xue Wu, Yabin Guo","doi":"10.62347/ZZPA6435","DOIUrl":"10.62347/ZZPA6435","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the synergistic interaction between polycystic ovary syndrome (PCOS) and metabolic syndrome (MetS) in relation to the risk of endometrial cancer (EC). Additionally, we aimed to develop a clinically applicable, high-risk early-warning model that incorporates these interactive factors, enhancing the precision and clinical utility of EC screening.</p><p><strong>Methods: </strong>We conducted a retrospective case-control study involving 445 newly diagnosed EC patients and 299 healthy female controls from the First People's Hospital of Changde City, between January 2018 and January 2025. Multivariate logistic regression was used to assess the independent and combined effects of PCOS and MetS on EC risk. A nomogram-based predictive model was developed and validated rigorously using training, internal validation, and external validation cohorts. The model's performance was evaluated based on discrimination (area under the curve [AUC]), calibration (Hosmer-Lemeshow test), and clinical utility (decision curve analysis). The diagnostic performance of our comprehensive model was compared to traditional tumor markers (cancer antigen 125/199, human epididymis protein 4).</p><p><strong>Results: </strong>LASSO regression identified 14 clinically significant predictors. Logistic regression revealed that HE4 levels, endometrial thickness, and fasting blood glucose were independent risk factors for EC, while high-density lipoprotein was an independent protective factor. The nomogram based on these variables demonstrated excellent discrimination, with AUCs of 0.984 in the training set, 0.987 in the internal validation set, and 0.964 in the external validation set. The integrated risk model significantly outperformed individual markers in diagnostic accuracy across all datasets (P<0.001).</p><p><strong>Conclusion: </strong>Our PCOS-MetS interaction-based EC risk prediction model showed robust and consistent performance across multiple validation cohorts. This tool significantly improves early detection accuracy and holds substantial clinical promise, laying the foundation for personalized EC risk management strategies.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3376-3394"},"PeriodicalIF":2.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adora1 promotes colon cancer immune evasion via Irf1-PD-L1 signal axis.","authors":"Yubin Wang, Yilin Zeng, Peizhong Chen, Boming Xu, Xiaoqiang Liu, Zhijun Su","doi":"10.62347/ADLH2257","DOIUrl":"10.62347/ADLH2257","url":null,"abstract":"<p><p>Immunotherapy targeting immune checkpoints such as programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) has emerged as a novel treatment option for various cancers, including colon cancer. However, immune evasion mechanisms can limit the efficacy of cancer immunotherapy. Understanding the regulatory mechanisms of PD-1/PD-L1 expression is therefore critical to enhancing immunotherapeutic outcomes. A previous study demonstrated that the adenosine A1 receptor (Adora1) regulates PD-L1 expression and tumor immune evasion in human melanoma; however, its role in colon cancer and associated immune escape remains poorly defined. To investigate this, we downregulated Adora1 expression in CT26 colon cancer cells using lentiviral transduction of Adora1-targeting shRNA. We assessed Adora1 and PD-L1 expression levels and evaluated cell proliferation in CT26 cells. <i>In vivo</i>, we inoculated CT26 cells into mice and monitored tumor growth, immune cell phenotypes, and T cell exhaustion within the tumors. Additionally, we evaluated T cell exhaustion <i>in vitro</i> by co-culturing T cells with CT26 cells. While Adora1 knockdown did not impact CT26 cell viability or proliferation <i>in vitro</i>, it significantly suppressed tumor growth <i>in vivo</i> (P<0.0001). Furthermore, Adora1 downregulation reduced T cell exhaustion (all P=0.0025) by decreasing PD-L1 expression in CT26 cells. Knockdown of Adora1 did not alter Atf3 expression but led to reduced Irf1 expression (P=0.0268), which contributed to the downregulation of PD-L1. Overall, these findings suggest that Adora1 downregulation inhibits immune escape in colon cancer by suppressing PD-L1 expression.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3500-3509"},"PeriodicalIF":2.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and validation of a nomogram for predicting 90-day mortality in patients with advanced lung cancer based on inflammatory and nutritional biomarkers.","authors":"Zanqin Wang, Wenzhen Xun, Xiangxing Ma, Sicong Jiang, Caijin Jin","doi":"10.62347/RNYP8960","DOIUrl":"10.62347/RNYP8960","url":null,"abstract":"<p><p>This retrospective study of 455 stage III/IV non-small cell lung cancer patients treated at Sanmen People's Hospital from January 2022 to January 2025 aimed to identify prognostic factors for short-term mortality and develop a validated nomogram for risk assessment. Patients were divided into training (n = 318) and validation (n = 137) cohorts, with clinical and laboratory variables - age, body mass index, Eastern Cooperative Oncology Group (ECOG) performance status, chronic obstructive pulmonary disease (COPD), C-reactive protein (CRP), interleukin-6 (IL-6), serum albumin (ALB), and lactate dehydrogenase (LDH) - analyzed using Kolmogorov-Smirnov tests for data distribution, and t-tests, Mann-Whitney U tests, and chi-square tests for comparisons. Logistic regression identified CRP ≥ 24.42 mg/L (odds ratio = 6.285, P = 0.002), IL-6 ≥ 28.705 pg/mL (odds ratio = 38.364, P < 0.001), and LDH ≥ 357 U/L (odds ratio = 10.132, P < 0.001) as predictors of increased mortality risk, while ALB ≥ 32.65 g/L (odds ratio = 0.073, P < 0.001) and ECOG score = 0 (odds ratio = 0.214, P = 0.040) were associated with reduced risk. Cox regression confirmed CRP, IL-6, ALB, LDH, and COPD as significant predictors. A nomogram constructed from these factors showed strong performance, with area under the curve values of 0.932, 0.930, and 0.962 for 30-, 60-, and 90-day mortality in the training cohort, and 0.894, 0.916, and 0.925 in the validation cohort, respectively, alongside concordance indices of 0.922 (training) and 0.877 (validation). Decision curve analysis and calibration plots confirmed robust clinical applicability and prognostic precision, establishing the nomogram as a reliable tool for personalized risk stratification in advanced lung cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3570-3587"},"PeriodicalIF":2.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432572/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes of dabrafenib plus trametinib in locally advanced or metastatic BRAF V600E-mutant papillary thyroid cancer.","authors":"Yen-Hao Chen, Chen-Kai Chou, Shun-Yu Chi, Yen-Hsiang Chang, Pei-Wen Wang, Yi-Chia Chan","doi":"10.62347/WFPD3948","DOIUrl":"10.62347/WFPD3948","url":null,"abstract":"<p><p>BRAF V600E is the most common oncogenic mutation in papillary thyroid carcinoma (PTC). This study aimed to assess the clinical outcomes of combining dabrafenib and trametinib in patients with BRAF V600E-mutant PTC. Patients with BRAF V600E-mutant PTC treated with dabrafenib and trametinib in either first-line or second-line settings were included. Dabrafenib was administered orally at 150 mg twice daily, alongside trametinib at 2 mg once daily. Response was determined using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A total of 71 PTC patients who received systemic therapy were identified, including 21 patients who experienced dabrafenib plus trametinib. For these 21 patients, the objective response rate (ORR) was 66.7%, with a disease control rate (DCR) of 85.7%. In the first-line setting, the ORR and DCR were higher at 75.0% and 91.7%, respectively. The median progression-free survival (PFS) was 40.7 months, and the overall survival (OS) was 47.7 months. While patients treated in the first-line setting (n=12) showed better PFS (40.7 months vs. 18.9 months) and OS (47.7 months vs. 39.4 months) compared to those treated in the second-line setting (n=9), the differences were not statistically significant. Moreover, in the first-line treatment, 12 patients received dabrafenib plus trametinib, while 59 patients were treated with lenvatinib; no significant differences in PFS or OS were observed between the two groups. Most adverse events related to the combination therapy were grade 1-2, with no grade 3-4 toxicities reported. Additionally, most patients (75.0%) were able to receive subsequent treatments following disease progression to this combination therapy. The findings of current study highlight the efficacy and safety of dabrafenib combined with trametinib in patients with BRAF V600E-mutant PTC, particularly as a first-line treatment. These findings suggest a promising therapeutic option for this patient population.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"15 8","pages":"3524-3532"},"PeriodicalIF":2.9,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145063147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}