American journal of cancer research最新文献

{"title":"Erratum: Endogenous HMGB1 regulates GSDME-mediated pyroptosis via ROS/ERK1/2/caspase-3/GSDME signaling in neuroblastoma.","authors":"Chen-Ying Fan, Fang-Hua Ye, Min Peng, Jia-Jia Dong, Wen-Wen Chai, Wen-Jun Deng, Hui Zhang, Liang-Chun Yang","doi":"10.62347/BEXD5889","DOIUrl":"https://doi.org/10.62347/BEXD5889","url":null,"abstract":"<p><p>[This corrects the article on p. 436 in vol. 13, PMID: 36895972.].</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2671-2674"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373551/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468390","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":"Kang Ru Plus reverses osimertinib resistance in lung adenocarcinoma via suppression of EGFR/PI3K/AKT signaling.","authors":"Thomas G Mhone, Wei-Wen Kuo, Chih-Ying Chi, Chia-Hua Kuo, Tsung-Jung Ho, Yu-Ling Wu, Yueh-Min Lin, Ming-Cheng Chen, Chih-Yang Huang, Shinn-Zong Lin","doi":"10.62347/CURF9339","DOIUrl":"10.62347/CURF9339","url":null,"abstract":"<p><strong>Background: </strong>Acquired resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors such as osimertinib remains a major challenge in the treatment of EGFR-mutant non-small cell lung cancer (NSCLC). Multi-component natural product therapies may provide complementary strategies capable of modulating multiple signaling pathways involved in therapeutic resistance. This study investigated the pharmacological activity of Kang Ru Plus (KR-Plus), a multi-herb formulation, and evaluated its ability to enhance sensitivity to osimertinib in resistant lung adenocarcinoma models.</p><p><strong>Methods: </strong>The anti-proliferative and chemosensitizing effects of KR-Plus were assessed in EGFR-mutant lung adenocarcinoma cells and osimertinib-resistant derivatives using MTT assays, flow cytometry, immunofluorescence, and Western blot. Phytochemical composition was characterized by UHPLC-QTOF-MS-based metabolite profiling. Network pharmacology and molecular docking analyses were performed to predict potential targets and pathways. In vivo efficacy was evaluated in H1975-OSR xenograft mouse models.</p><p><strong>Results: </strong>KR-Plus inhibited cell proliferation across multiple cancer cell lines and significantly enhanced the cytotoxic effects of osimertinib in resistant lung adenocarcinoma cells. Mechanistically, KR-Plus reduced EGFR phosphorylation and suppressed downstream PI3K/AKT, ERK, and mTOR signaling, resulting in cell-cycle arrest and apoptosis. Metabolite profiling identified several flavonoids and phenolic compounds with predicted interactions within EGFR-associated signaling networks. In xenograft models, combined treatment with KR-Plus and osimertinib markedly suppressed tumor growth and improved survival without evident systemic toxicity.</p><p><strong>Conclusion: </strong>KR-Plus exerts multi-target effects that disrupt EGFR-driven survival signaling and enhance responsiveness to osimertinib in resistant lung adenocarcinoma models. These findings support the potential of polyherbal formulations as complementary strategies to overcome resistance to targeted therapies.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2389-2406"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468368","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":"Robot-assisted radical prostatectomy reduces biochemical recurrence risk and improves urinary continence recovery compared with laparoscopic approach in high-risk localized prostate cancer after neoadjuvant therapy: a real-world propensity score-matched analysis.","authors":"Xing Zheng, Xi Huang, Weijin Zheng, Jianfeng Zhao, Jun Fu","doi":"10.62347/WCPI7800","DOIUrl":"10.62347/WCPI7800","url":null,"abstract":"<p><p>This retrospective study compared the oncological and functional outcomes of robot-assisted radical prostatectomy (RARP) versus laparoscopic radical prostatectomy (LRP) in 523 patients with high-risk localized prostate cancer (HR-LPC) receiving neoadjuvant therapy (NAT). After 1:1 propensity score matching (PSM), 218 patients per group were included. Multivariate Cox regression confirmed that RARP was independently associated with a significantly lower biochemical recurrence (BCR) risk compared with LRP (after PSM: HR=0.626, 95% CI 0.471-0.833, P=0.001), a finding that remained robust across all sensitivity analyses. Subgroup analyses identified significant BCR protection by RARP in patients with preoperative PSA ≥20 ng/mL (P=0.001), pathological T stage pT2-pT3a (P=0.002), biopsy ISUP grade 4 (P=0.005), negative lymph nodes (P<0.001), ADT monotherapy (P=0.007), and age ≥65 years (P=0.002), with no significant heterogeneity across subgroups (all P-interaction >0.05). RARP also demonstrated perioperative advantages over LRP, including less intraoperative blood loss (median 239.5 vs. 399.5 mL, P<0.001), lower transfusion rate (4.59% vs. 12.39%, P=0.003), and shorter hospital stay (median 7 vs. 9 days, P<0.001), while pathological outcomes were comparable between groups (all P>0.05). Regarding functional recovery, RARP achieved significantly higher urinary continence rates at postoperative months 1 (33.5% vs. 21.1%, P=0.005), 3 (53.2% vs. 38.5%, P=0.003), 6 (74.8% vs. 60.6%, P=0.002), and 12 (84.9% vs. 73.9%, P=0.006), with a median continence recovery time of 3 months versus 6 months in the LRP group (P<0.001). These findings suggest that RARP offers meaningful oncological and functional advantages over LRP in HR-LPC patients undergoing NAT.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2232-2257"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373561/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468220","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":"DDOST mediates cervical cancer cell malignant progression by interacting with SMARCA4.","authors":"Biqing Zhu, Yizhi Ge, Yuxuan Wen, Yinan Wu, Jinjie Yao, Jing Luo, Jing Wu, Dongfang Dai","doi":"10.62347/JJQH4316","DOIUrl":"10.62347/JJQH4316","url":null,"abstract":"<p><p>DDOST is generally recognized as a regulator of glycosylation homeostasis and its deficiency can cause congenital glycosylation disorders. However, its role in tumors has not yet been elucidated. This study aimed to explore the functional role of DDOST and its related mechanisms in cervical cancer (CC). The clinical correlation of DDOST was analyzed using The Cancer Genome Atlas (TCGA) database and verified by immunohistochemistry slides of clinical samples. Cell growth, proliferation, apoptosis, migration, and invasion were evaluated. Co-immunoprecipitation (co-IP) and liquid chromatography with tandem mass spectrometry (LC-MS) were used to identify interacting proteins. The functions of the interacting proteins were further confirmed using genetic rescue experiments. A subcutaneous xenograft model was used to investigate tumorigenesis. Based on the TCGA data and our collected clinical samples, we found that DDOST was associated with a more aggressive pathological phenotype. DDOST also promoted several malignant phenotypes in CC cells. Co-IP coupled with LC-MS identified the interacting protein SMARCA4, and western blotting confirmed a positive interaction between these two proteins. Similar to in vivo tumorigenesis, cell growth and migration were markedly rescued by SMARCA4 overexpression after DDOST knockdown, as was tumorigenesis <i>in vivo</i>. This study showed that DDOST promoted tumorigenesis in CC and was identified it as a possible novel biomarker or therapeutic target in CC. The interaction between DDOST and SMARCA4 is a potential mechanism that requires further investigation.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2377-2388"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373567/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468242","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":"Serum USP1 and PD-L1 levels independently predict treatment response and prognosis in cervical cancer: a retrospective cohort study.","authors":"Yingge Zhao, Hairong Zhou","doi":"10.62347/MQAJ5228","DOIUrl":"10.62347/MQAJ5228","url":null,"abstract":"<p><p>Cervical cancer remains a common malignant tumor with highly variable treatment outcomes, and the combined predictive value of serum ubiquitin-specific protease 1 (USP1) and programmed death ligand 1 (PD-L1) has been rarely investigated. This retrospective study included 102 cervical cancer patients treated between July 2022 and July 2024, who were classified into treatment-sensitive and treatment-resistant groups according to RECIST 1.1 criteria. After propensity score matching (1:1, caliper 0.02) for age, FIGO (International Federation of Gynecology and Obstetrics) stage, tumor diameter, lymph node status, and serum biomarkers, 84 patients (42 per group) were analyzed. Serum USP1 and soluble PD-L1 levels were measured by ELISA, and logistic regression, Kaplan-Meier curves, and Cox models were used for analysis. The resistant group showed significantly higher USP1 (38.62±9.43 vs. 29.86±8.24 pg/mL, <i>P</i> < 0.001) and PD-L1 levels (156.48±42.78 vs. 124.58±38.92 pg/mL, <i>P</i> < 0.001), with a positive correlation between the two (r = 0.51, <i>P</i> < 0.001), which remained significant after adjustment (partial r = 0.42, <i>P</i> = 0.002). Multivariable analysis identified high USP1 (OR = 2.56, 95% CI: 1.34-4.89) and high PD-L1 (OR = 2.18, 95% CI: 1.15-4.13) as independent predictors of poor treatment response, and both were independent risk factors for overall survival (USP1: HR = 2.18, 95% CI: 1.24-3.83; PD-L1: HR = 1.96, 95% CI: 1.12-3.43). No significant interaction was found between the two markers (<i>P</i> > 0.05), indicating additive rather than synergistic effects. Combining both biomarkers improved predictive accuracy with a C-index of 0.74 and an NRI of 31%. In conclusion, pre-treatment serum USP1 and soluble PD-L1 levels are effective indicators for predicting treatment response and prognosis in cervical cancer, and their combined assessment helps identify high-risk patients and supports personalized treatment planning.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2458-2480"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373547/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468222","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":"Advances in ferroptosis research in ovarian cancer: molecular mechanisms and therapeutic perspectives.","authors":"Yingdi Han, Xinyu Shen, Kaikai Wang, Linzhu Li, Yufei Yang, Shafinah Ahmad Suhaimi, Yali Wei, Wenzhi Zhang, Kai Sun, Zhaoyu Li, Haoling Zhang, Doblin Sandai, Yu He","doi":"10.62347/GATT6898","DOIUrl":"10.62347/GATT6898","url":null,"abstract":"<p><p>Ovarian cancer is one of the most aggressive malignancies in the female genital system and presents a poor prognosis. Its high rate of recurrence and emergence of acquired resistance to the current chemotherapeutic approaches significantly restrict its long-term therapeutic efficacy. While treatment strategies including cytoreductive surgery (CRS) plus platinum (Pt)-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARP inhibitors) have brought clinical benefits to a proportion of patients, the majority eventually suffer cancer relapse post-treatment. This finding suggests that classical forms of cell death may not fully explain treatment outcomes, survival, and resistance in ovarian cancer. Ferroptosis is a nonapoptotic mode of cell death that results from the iron-dependent and lethal peroxidation of lipids. Its onset and progression are contextually regulated by iron homeostasis, lipid metabolism, and redox balance, and also tightly involved in the tumor metabolic reprogramming and adaptation to the tumor microenvironment (TME). Under therapeutic pressure, ovarian cancer cells may become more susceptible to ferroptosis while simultaneously suppressing ferroptotic cell death through multilayered regulatory systems, including glutathione peroxidase 4 (GPX4) and the cystine/glutamate antiporter system (system Xc^-) antioxidant defenses, acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated lipid peroxidation (LPO), and nuclear receptor coactivator 4 (NCOA4)-dependent ferritinophagy, in order to survive. This biphasic behaviour is strongly linked to treatment resistance and disease recurrence. In this review, the molecular mechanisms by which ferroptosis operates in ovarian cancer are systematically reviewed, and a profile of regulatory factors - genetic, epigenetic, metabolic, and microenvironmental - is presented. Special attention is given to a summary of current literature on the cross-talk between ferroptosis and the sensitivity of Pt-based chemotherapy and PARP inhibitors, cancer stem cell properties within ovarian cancer, as well as the TME. In addition, the current progress in ferroptosis-inducing strategies, nanodelivery systems, and related biomarkers for precision therapy and therapeutic response prediction is comprehensively discussed.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2407-2432"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468317","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":"Time-dependent evolution of osteosarcoma recurrence risk across clinical risk stratification and its prognostic value.","authors":"Huadong Zhang, Xingxing Wang, Xiaochen Qiao, Chaojian Xu, Yi Feng","doi":"10.62347/TPOL1062","DOIUrl":"10.62347/TPOL1062","url":null,"abstract":"<p><strong>Background: </strong>Patients with osteosarcoma remain at high risk of recurrence after surgery despite multimodal treatment, and previously developed prediction models have rarely considered the time-varying effects of prognostic factors.</p><p><strong>Methods: </strong>We retrospectively analyzed 498 patients with osteosarcoma who received standard treatment at two centres between 2010 and 2019, including a training cohort (n = 341) and an external validation cohort (n = 157). The proportional hazards assumption was assessed using Schoenfeld residuals. For variables with time-dependent effects, piecewise Cox regression models were used. A dynamic prediction model was developed and evaluated using the concordance index, time-dependent receiver operating characteristic curves, calibration curves, and decision curve analysis.</p><p><strong>Results: </strong>During a median follow-up of 52.0 months, 202 patients (40.6%) developed postoperative recurrence, with most recurrences occurring within 12.0 months after surgery. Multivariable analysis showed that axial location, tumor diameter ≥ 10 cm, Huvos grade I-II, positive surgical margins, and incomplete adjuvant chemotherapy were independent risk factors. Time-dependent analyses showed that the effects of these covariates were strongest during 12.0-24.0 months postoperatively and then declined, becoming non-significant beyond 36.0 months in most cases. The one-, three-, and five-year area under the curve values were 0.805, 0.734, and 0.923 in the training cohort and 0.860, 0.775, and 0.890 in the validation cohort, respectively. Risk scores stratified patients into low-, intermediate-, and high-risk groups, with significantly different recurrence-free survival (P < 0.0001).</p><p><strong>Conclusion: </strong>This dynamic prediction model showed good discriminatory ability and generalizability and may support risk-adapted surveillance, especially within 12-24 months after surgery.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2189-2214"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468181","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":"UBE2J2-mediated ubiquitination modification of MCM6 regulates proliferation and migration of cervical cancer cells.","authors":"Yanfeng Guo, Yan Zhang, Shuai Zhang, Jingyu Guo, Libing Huang, Zixi Wang, Jiateng Zhong, Hongyan Zhou","doi":"10.62347/SHIF8882","DOIUrl":"10.62347/SHIF8882","url":null,"abstract":"<p><p>Microchromosome maintenance protein 6 (MCM6), a member of the MCM family, is involved in the regulation of various cancer progression. However, the role and related regulatory mechanisms in cervical cancer are unclear. The aim of this study was to investigate the role of MCM6 in cervical cancer and the regulation of MCM6 protein homeostasis by the ubiquitin-conjugating enzyme E2J2 (UBE2J2). To investigate the expression and function of MCM6 in cervical cancer, we used RT-qPCR and Western blot and found that MCM6 was upregulated. Cell function experiments indicate that MCM6 promotes the proliferation and migration of cervical cancer cells. The GEPIA database identified co-expressed genes with MCM6, and KEGG enrichment analysis showed that MCM6 was significantly associated with UBE2J2. We performed molecular docking of proteins and identified amino acid residues involved in the MCM6-UBE2J2 interaction. Using co-immunoprecipitation and Immunofluorescence experiments, we found that MCM6 binds to UBE2J2 and localizes to the nucleus. Ubiquitination experiments demonstrated that UBE2J2 mediates MCM6 ubiquitination. Response experiments showing that UBE2J2-mediated MCM6 ubiquitination modification regulates the proliferation and migration of cervical cancer cells. Our results suggest that the UBE2J2-MCM6 axis plays an important role in regulating cervical cancer proliferation and migration and is a promising therapeutic target for its treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2355-2366"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468232","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":"Prognostic value of salt-inducible kinase 2 expression in advanced hepatocellular carcinoma treated with sorafenib or lenvatinib: a propensity score-matched cohort study.","authors":"Qinghai Fu, Xiaolong Wang, Shiqin Zheng, Wei Wang","doi":"10.62347/DCCQ4239","DOIUrl":"10.62347/DCCQ4239","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) requires reliable biomarkers to guide the use of sorafenib or lenvatinib for personalized first-line treatment. This study investigated the association between salt-inducible kinase 2 (SIK2) expression and treatment outcomes in patients with advanced HCC receiving these tyrosine kinase inhibitors (TKIs). A retrospective cohort of 120 patients who received treatment from January 2022 to December 2024 was included. The expression of SIK2 was evaluated by immunohistochemistry, and the optimal H-score cut-off value of 6 was determined by ROC analysis. After 1:1 propensity score matching, 47 patients with high SIK2 expression and 47 patients with low SIK2 expression were compared. Patients with high SIK2 expression showed a significantly superior objective response rate (36.2% vs. 12.8%, P<0.001) and disease control rate (87.2% vs. 57.4%, P<0.001), as well as prolonged median overall survival (15.4 vs. 9.5 months; HR = 0.30, P<0.001) and progression-free survival (7.8 vs. 3.7 months; HR = 0.38, P<0.001). Multivariate analysis confirmed that low SIK2 expression was an independent predictor of poor OS (adjusted HR = 2.22, P<0.05) and PFS (adjusted HR = 1.96, P<0.05). Subgroup analysis showed that the prognostic value of SIK2 was consistent in the sorafenib and lenvatinib groups, and there was no significant interaction (P for interaction >0.05). Safety analysis showed that the incidence of adverse events between the two groups was comparable, while patients with low SIK2 expression had significant increases in liver enzymes and bilirubin after treatment (all P<0.05). In conclusion, low SIK2 expression independently predicts poor therapeutic response and survival in advanced HCC patients receiving first-line sorafenib or lenvatinib, with consistent predictive value across both TKIs. SIK2 represents a promising common predictive biomarker to guide personalized first-line targeted therapy for HCC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2503-2517"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468340","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":"Targeting ferroptosis in gefitinib-resistant HCC827 NSCLC cells using erastin.","authors":"A-Young Nam, Sang Hoon Joo, Na Yeong Lee, Goo Yoon, Jin Woo Park, Jung-Hyun Shim","doi":"10.62347/QRAD4785","DOIUrl":"10.62347/QRAD4785","url":null,"abstract":"<p><p>Overcoming drug resistance remains essential for improving clinical outcomes in non-small cell lung cancer (NSCLC). This study explores the differential susceptibility of drug-resistant cancer cells, utilizing gefitinib (GEF)-resistant HCC827GR NSCLC cells as a model system. We observed that HCC827GR cells inherently display elevated levels of reactive oxygen species (ROS) and increased expression of ferroptosis-related markers when compared with GEF-sensitive cells. Accordingly, the HCC827GR lineage showed heightened responsiveness to erastin-mediated cytotoxicity, as determined by MTT and soft-agar assays. Our mechanistic investigations established that erastin treatment resulted in non-apoptotic cell death, accompanied by mitochondrial dysfunction and G2/M phase arrest in the cell cycle. In-depth analysis demonstrated that erastin notably raised intracellular iron and ROS concentrations and induced lipid peroxidation. Pretreatment with N-acetyl cysteine (NAC) validated the crucial involvement of ROS, and the use of ferrostatin-1 conclusively verified ferroptosis as the predominant mode of cell death. In summary, GEF-resistant HCC827GR cells exhibit increased sensitivity to erastin-induced ferroptosis compared with the parental line. This distinct vulnerability should be further studied as a potential therapeutic approach for targeting drug-resistant NSCLC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"16 6","pages":"2342-2354"},"PeriodicalIF":3.1,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13373552/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468193","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}