Oncotarget最新文献

{"title":"Nerofe+ldDox releases c-Jun from nuclear ST2 to reprogram the immune microenvironment in mtKRAS tumors.","authors":"Joel Ohana, Uziel Sandler, Benjamin A Weinberg, Stephen Liu, Yoram Devary","doi":"10.18632/oncotarget.28820","DOIUrl":"10.18632/oncotarget.28820","url":null,"abstract":"<p><strong>Background/objectives: </strong>Mutant KRAS (mtKRAS) tumors are highly immunosuppressive, largely through secretion of IL-10 and TGF-β2, which prevent immune cell infiltration. Nerofe (dTCApFs), a peptide derivative of Tumor Cell Apoptosis Factor, induces endoplasmic reticulum stress and modulates immune signaling through the T1/ST2 receptor, which is overexpressed in mtKRAS tumors. We evaluated whether combining Nerofe with low-dose doxorubicin (ldDox) could remodel the immune microenvironment and overcome tumor immunosuppression.</p><p><strong>Methods: </strong><i>In vitro</i> experiments were performed in PANC-1 pancreatic adenocarcinoma cells harboring a KRAS mutation. Cytokine expression, c-Jun activity, and c-Jun-ST2 binding were measured by western blotting, immunocytochemistry, and immunoprecipitation. In a clinical trial (NCT05661201), patients with mtKRAS tumors received weekly Nerofe (288 mg/m²) plus ldDox (8 mg/m²). Tumor biopsies were analyzed by immunohistochemistry before treatment and after 7 weeks.</p><p><strong>Results: </strong>Nerofe+ldDox treatment increased IL-2 and suppressed IL-10 in PANC-1 cells, reversing the immunosuppressive cytokine profile. Patient biopsies confirmed these effects, showing higher IL-2, lower IL-10, and increased infiltration of NK cells, CD8⁺ cytotoxic T lymphocytes, and CD4⁺ helper T cells. KRAS protein levels were reduced in post-treatment biopsies. Mechanistically, Nerofe+ldDox elevated total c-Jun protein but reduced phosphorylation at Ser63 and Ser73. Co-immunoprecipitation showed that c-Jun was bound to nuclear ST2 under basal conditions; this complex was disrupted within 3 h of treatment, releasing c-Jun to activate IL-2 and miR-217 transcription before re-forming after 24 h. This transient release corresponds to the early induction of IL-2 and later reduction in KRAS levels.</p><p><strong>Conclusions: </strong>Nerofe+ldDox reprograms the immune microenvironment of mtKRAS tumors by releasing c-Jun from inhibitory nuclear ST2, enabling expression of IL-2 and miR-217. This \"nuclear immunomodulation\" promotes immune cell infiltration and downregulates KRAS expression, highlighting Nerofe+ldDox as a promising therapeutic approach for mtKRAS-driven cancers.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"848-857"},"PeriodicalIF":0.0,"publicationDate":"2025-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12750723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine learning-based survival prediction in colorectal cancer combining clinical and biological features.","authors":"Lucas M Vieira, Natasha A N Jorge, João B Sousa, João C Setubal, Peter F Stadler, Maria E M T Walter","doi":"10.18632/oncotarget.28783","DOIUrl":"10.18632/oncotarget.28783","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common and lethal types of cancer worldwide. Understanding both the biological and clinical aspects of the patient is essential to uncover the mechanism underlying the prognosis of the disease. However, most current approaches focus primarily on clinical or biological elements, which can limit their ability to capture the full complexity of the prognosis of CRC. This study aims to enhance understanding of the mechanisms of CRC by combining clinical and biological data from CRC patients with machine learning techniques (ML) to explore the importance of features and predict patient survival. First, we performed differential expression analysis and inspected patient survival curves to identify relevant biological features. Then, we applied ML techniques to understand the individual impact of each clinical and biological feature on patient survival. <i>E2F8</i>, <i>WDR77</i>, and <i>hsa-miR-495-3p</i> stood out as biological features, while pathological stage, age, new tumor event, lymph node count, and chemotherapy have shown themselves as interesting clinical features. Furthermore, our ML model achieved an accuracy of 89.58% to predict patient survival. The clinical and biological features proposed here in conjunction with ML can improve the interpretation of CRC mechanisms and predict patient survival.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"834-847"},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12714322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145768491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Exosome mediated miR-155 delivery confers cisplatin chemoresistance in oral cancer cells via epithelial-mesenchymal transition.","authors":"Prathibha Kirave, Piyush Gondaliya, Bhagyashri Kulkarni, Rakesh Rawal, Rachana Garg, Alok Jain, Kiran Kalia","doi":"10.18632/oncotarget.28782","DOIUrl":"10.18632/oncotarget.28782","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"815-817"},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758159/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Chikusetsu saponin IVa ameliorates high fat diet-induced inflammation in adipose tissue of mice through inhibition of NLRP3 inflammasome activation and NF-κB signaling.","authors":"Chengfu Yuan, Chaoqi Liu, Ting Wang, Yumin He, Zhiyong Zhou, Yaoyan Dun, Haixia Zhao, Dongming Ren, Junjie Wang, Changcheng Zhang, Ding Yuan","doi":"10.18632/oncotarget.28781","DOIUrl":"10.18632/oncotarget.28781","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"814"},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A personal perspective of patient-centred clinical trials.","authors":"Trevor Tyne, Elizabeth Ivimey, Leanne Duggan, Jia Liu","doi":"10.18632/oncotarget.28776","DOIUrl":"10.18632/oncotarget.28776","url":null,"abstract":"<p><p>Key objective: To illustrate the first-hand journey of three early phase trial participants highlighting their benefits and challenges of participation and patient-centric innovations required to improve trial experience. Knowledge generated: Early phase trials have traditionally centred on dose-finding and toxicity. However as they have increased in number and improved in therapeutic intent, the patient experience becomes increasingly important. This article illustrates benefits of participation including access to novel therapies, support and close monitoring but challenges around eligibility criteria, finances, and communication. Proposed solutions including trial navigators, enhanced communication training, and greater flexibility in enrolment criteria to improve trials access.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"808-812"},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanism of anticancer action of <i>bifidobacterium</i>: Insights from gut microbiota.","authors":"Hoang Do, Esther Asiamah, Mayanijesu Olorife, Arathi Pillai, Sakshi Patel, Ponniah Selvakumar, Sidhartha D Ray, Ashakumary Lakshmikuttyamma","doi":"10.18632/oncotarget.28779","DOIUrl":"10.18632/oncotarget.28779","url":null,"abstract":"<p><p><i>Bifidobacterium</i> has captured major attention recently because of its health benefits and extensive research highlighting its potential in cancer treatment and prevention. Evidence suggests that <i>bifidobacterium</i> can actively fight against various types of cancer, including those of the colon, lungs, breast, and stomach. Research indicates that several species of <i>bifidobacterium</i> can potentiate the action of chemotherapy, immunotherapy and radiation therapy in battling tumors, and reducing their adverse effects. Bifidobacteria shows its multipronged effect by modulating various immunomodulatory and inflammatory signaling pathways, potentially leading to the suppression of tumor growth. Moreover, different species of bifidobacteria are known to regulate signaling molecules involved in promoting apoptosis. In addition, bifidobacteria have an impact on the regulation of diverse microRNAs. The anticancer properties of <i>bifidobacterium</i> may also stem from its ability to detoxify carcinogens and transform dietary elements. This review also covers how dietary factors can influence the prevalence of <i>bifidobacterium</i> in the gut, further affecting its anticancer capabilities.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"818-833"},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: Protective effect of tanshinone IIA against cardiac hypertrophy in spontaneously hypertensive rats through inhibiting the Cys-C/Wnt signaling pathway.","authors":"Jun Feng, Hua-Wen Chen, Li-Juan Pi, Jin Wang, Da-Qian Zhan","doi":"10.18632/oncotarget.28780","DOIUrl":"10.18632/oncotarget.28780","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"813"},"PeriodicalIF":0.0,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12758157/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Enhanced proteasomal activity is essential for long term survival and recurrence of innately radiation resistant residual glioblastoma cells.","authors":"Jacinth Rajendra, Keshava K Datta, Sheikh Burhan Ud Din Farooqee, Rahul Thorat, Kiran Kumar, Nilesh Gardi, Ekjot Kaur, Jyothi Nair, Sameer Salunkhe, Ketaki Patkar, Sanket Desai, Jayant Sastri Goda, Aliasgar Moiyadi, Amit Dutt, Prasanna Venkatraman, Harsha Gowda, Shilpee Dutt","doi":"10.18632/oncotarget.28778","DOIUrl":"10.18632/oncotarget.28778","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"791-792"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12598637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction: <i>PDHA1</i> gene knockout in prostate cancer cells results in metabolic reprogramming towards greater glutamine dependence.","authors":"Yaqing Li, Xiaoran Li, Xiaoli Li, Yali Zhong, Yasai Ji, Dandan Yu, Mingzhi Zhang, Jian-Guo Wen, Hongquan Zhang, Mariusz Adam Goscinski, Jahn M Nesland, Zhenhe Suo","doi":"10.18632/oncotarget.28777","DOIUrl":"10.18632/oncotarget.28777","url":null,"abstract":"","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"790"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12598633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LRIG1-3 in gliomas: LRIG1 protein expression decreased in higher grade gliomas.","authors":"Marlene Happe, Saskia Kuhl, Lukas Görtz, Roland Goldbrunner, Marco Timmer","doi":"10.18632/oncotarget.28775","DOIUrl":"10.18632/oncotarget.28775","url":null,"abstract":"<p><p>The LRIG gene family consists of LRIG1-3. While LRIG2 has been described as a tumor promoter, LRIG1 and LRIG3 have been identified as tumor suppressors in previous literature. Because of these contrasting roles, the expression of LRIG1-3 was examined across different grades of glioma, between primary and secondary glioblastoma and with focus on chemotherapy treatment. Human tumor tissue samples were extracted during neurosurgery and grouped among the WHO classification valid at the time of surgery. Quantitative western blot analysis, qPCR and immunofluorescence staining were performed. LRIG1 was less expressed in glioma compared to peritumoral tissue with additional decrease with ascending tumors grade. Further, secondary glioblastoma expressed more LRIG1 protein than primary. On mRNA level, the same was seen for LRIG2, were low grade glioma expressed significantly more LRIG2 than high grade glioma. And on protein level, secondary glioblastoma showed higher expression than primary. LRIG3 mRNA expression, in contrast, was significantly higher in grade II gliomas compared to surrounding control tissue, whereas chemotherapy did not significantly affect expression levels in glioblastoma. Our results reinforce suggestions that LRIG1-3 could function as diagnostic markers and therapeutic targets in the treatment of gliomas.</p>","PeriodicalId":19499,"journal":{"name":"Oncotarget","volume":"16 ","pages":"793-807"},"PeriodicalIF":0.0,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12598643/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145471722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}