Cancer letters最新文献

{"title":"SUMOylation of SND1 drives mature miRNA degradation and tumor progression","authors":"Yingting Cao ,&nbsp;Yanli Wang ,&nbsp;Xindi Zhang ,&nbsp;Yixin Zhang ,&nbsp;Xintong Zhang ,&nbsp;Xiaopeng Tan ,&nbsp;Lian Li ,&nbsp;Ran Chen ,&nbsp;Runhui Lu ,&nbsp;Ruiyu Xie ,&nbsp;Jianxiu Yu ,&nbsp;Xiaojing Zhao","doi":"10.1016/j.canlet.2026.218253","DOIUrl":"10.1016/j.canlet.2026.218253","url":null,"abstract":"<div><div>The global downregulation of microRNAs (miRNAs) is a hallmark of many cancers, yet the mechanisms governing mature miRNA degradation remain poorly understood. Post-translational modifications (PTMs) have emerged as key regulators of RNA metabolism. However, the specific role of stress-responsive PTMs in driving miRNA degradation within the complex stress landscape of the tumor microenvironment is a critical unanswered question. We demonstrate that the endonuclease SND1 is SUMOylated at K513 in response to stresses such as oxidative stress and Cisplatin. This inducible modification enhances the miRNA-degrading activity of SND1 by promoting its interaction with AGO2 and UPF1, thereby facilitating mature miRNA decay. A key consequence is the degradation of a novel tumor-suppressive miRNA, miR-chr5_25226, leading to elevated MAPK10 expression that fuels tumor cell proliferation, migration, and Cisplatin resistance. Functional rescue experiments confirmed that restoring miR-chr5_25226 or silencing MAPK10 reverses these oncogenic effects. Furthermore, the SUMOylation inhibitor 2-D08 effectively restored miR-chr5_25226 expression and sensitized tumor cells to Cisplatin. Together, our findings reveal a novel oncogenic axis in which stress-induced SUMOylation of SND1 links tumor microenvironment stress to miRNA degradation. This SUMO1–SND1/miR-chr5_25226/MAPK10 pathway identifies the targeting of SND1 SUMOylation as a potential therapeutic strategy to modulate oncogenic miRNA decay and enhance chemosensitivity.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218253"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitigating tumor heterogeneity in lung Cancer: A dual-targeted NIR-II imaging strategy for accurate tumor localization and intraoperative navigation","authors":"Yifeng Li ,&nbsp;Chao Li ,&nbsp;Yueqi Wang ,&nbsp;Jian Zhou ,&nbsp;Boyu Zhou ,&nbsp;Lan Mei ,&nbsp;HuiYong Niu ,&nbsp;Zhenhua Hu ,&nbsp;Jie Tian ,&nbsp;Changjian Li","doi":"10.1016/j.canlet.2026.218241","DOIUrl":"10.1016/j.canlet.2026.218241","url":null,"abstract":"<div><div>Precise localization and complete resection are critical for preventing recurrence in non-small cell lung cancer (NSCLC), yet these goals remain clinically challenging. The second near-infrared window (1000–1700 nm, NIR-II) fluorescent molecular imaging offers a promising solution, and single-targeted probes have been developed for intraoperative guidance. However, tumor heterogeneity often limits the efficacy of single-target antibody probes, resulting in low detection sensitivity. Therefore, this study aimed to evaluate a dual-targeting strategy simultaneously engaging EGFR and cMET for NIR-II-guided lung cancer surgery. Based on the higher overexpression of EGFR and cMET in NSCLC, we implemented the bispecific probe Amivantamab-IRDye800CW to establish a dual-targeting imaging strategy. After validating its superior properties and NIR-II imaging advantages, we assessed its tumor-targeting capability and surgical navigation potential through in vivo imaging. Additionally, freshly resected NSCLC specimens were incubated with probes to confirm target specificity. Amivantamab-IRDye800CW exhibited NIR-II fluorescence emission (up to 1500 nm), with improved imaging performance over NIR-I. In subcutaneous xenograft models, the probe demonstrated precise tumor targeting (tumor-to-background ratio = 6.79 ± 0.49) and enabled complete resection of both subcutaneous tumors and orthotopic lung tumors. The probe also retained strong targeting ability in patient-derived xenograft (PDX) models, which better preserve tumor heterogeneity. Furthermore, Amivantamab-IRDye800CW accurately localized cancerous tissues in clinical NSCLC specimens. These findings demonstrate that implementing a dual-targeting strategy in NSCLC, effectively reduces the impact of tumor heterogeneity on NIR-II imaging. This approach improves tumor localization precision and provides reliable intraoperative guidance, highlighting its strong potential for clinical translation in NSCLC surgery.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218241"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145898001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Updated clinical practice guidelines for the management of adult diffuse gliomas","authors":"Tao Jiang ,&nbsp;Do-Hyun Nam ,&nbsp;Zvi Ram ,&nbsp;Wai-sang Poo ,&nbsp;Jiguang Wang ,&nbsp;Damdindorj Boldbaatar ,&nbsp;Ying Mao ,&nbsp;Wenbin Ma ,&nbsp;Qing Mao ,&nbsp;Yongping You ,&nbsp;Chuanlu Jiang ,&nbsp;Xuejun Yang ,&nbsp;Vinay Tergaonkar ,&nbsp;Wei Zhang ,&nbsp;Zheng Wang ,&nbsp;Chunsheng Kang ,&nbsp;Xiaoguang Qiu ,&nbsp;Shaowu Li ,&nbsp;Ling Chen ,&nbsp;Xuejun Li ,&nbsp;Yu Wang","doi":"10.1016/j.canlet.2025.218185","DOIUrl":"10.1016/j.canlet.2025.218185","url":null,"abstract":"<div><div>It has been five years since the last version of the clinical practice guidelines for the management of adult diffuse gliomas was published by the Asian Glioma Genome Atlas (AGGA). Significant progress and revisions have occurred in the diagnosis and treatment of adult diffuse gliomas in recent years. In response to these updates, the joint guideline committee of the Chinese Glioma Cooperative Group (CGCG), the Society for Neuro-Oncology of China (SNO-China), and the Chinese Brain Cancer Association (CBCA) has revised the clinical practice guidelines. This updated guideline emphasizes molecular and pathological diagnostics, as well as the primary treatment modalities of surgery, radiotherapy, chemotherapy, and targeted therapy. Additionally, we have incorporated findings from recent clinical trials of new therapies to align with cutting-edge treatment strategies. This guideline is designed to serve as a practical resource for all professionals involved in managing adult diffuse glioma patients, while also providing valuable information for insurance companies and other institutions responsible for regulating cancer care costs in China and beyond.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218185"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fgl2-knockout tumor cells serve as a vaccine inducing long-duration brain-resident memory T cells that reject subsequent intracranial tumor cell challenges","authors":"Sheng Zhang ,&nbsp;Yining Jin ,&nbsp;Zhiliang Jia ,&nbsp;Xueqing Xia ,&nbsp;Yang Li ,&nbsp;Qi Wang ,&nbsp;Jing Wang ,&nbsp;Jian Wang ,&nbsp;Joya Chandra ,&nbsp;Gregory K. Friedman ,&nbsp;Shulin Li","doi":"10.1016/j.canlet.2025.218215","DOIUrl":"10.1016/j.canlet.2025.218215","url":null,"abstract":"<div><div>The failure to prevent brain tumors, including both recurrent primary and metastatic brain tumors, is the primary cause of patients’ mortality. We developed a novel whole tumor-cell vaccine to rapidly induce long-duration brain-resident memory T (T_RM) cells that prevent brain tumor progression. Ten Fgl2-KO primary and metastatic tumor cell lines, generated via CRISPR/Cas9, were used to vaccinate mice and for intracranial challenges with the WT tumor cells. Not only did vaccinated mice reject these tumor cell challenges, but also more than half of these mice became long-duration survivors. Transplanting brain immune cells from vaccinated mice into naïve mice enabled this rejection of intracranial challenges in the recipient mice, whereas depleting T_RM cells impaired it. Mechanistic studies uncovered that Fgl2 KO impaired the immunosuppressive molecule CD47; reconstitution of CD47 expression in Fgl2-KO tumor cells reversed the protection. Likewise, vaccination with CD47-knockdown tumor cells produced similar effects. Proteomic analysis found that Fgl2-KO–mediated suppression of CD47 occurred through the Src and PKCα pathways; inhibition of either pathway reduced CD47 expression. This study is the first to show that disrupting the Fgl2-CD47 circuit in tumor cells impairs their tumorigenic properties and induces long-term brain T_RM cells, thereby providing new strategies for improving the efficacy of currently used whole tumor-cell vaccines.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218215"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145741179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Baseline tumor-informed circulating tumor DNA concentration predicts early chemoimmunotherapy failure in diffuse large B-cell lymphoma","authors":"Qing Shi ,&nbsp;Muchen Zhang ,&nbsp;Yang He ,&nbsp;Ronggui Lin ,&nbsp;Mingci Cai,&nbsp;Huijuan Zhong,&nbsp;Shu Cheng,&nbsp;Pengpeng Xu,&nbsp;Weili Zhao,&nbsp;Li Wang","doi":"10.1016/j.canlet.2026.218249","DOIUrl":"10.1016/j.canlet.2026.218249","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218249"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT2 mitigates radiation-induced oral mucositis by promoting homologous recombination-mediated DNA double-strand break repair in epithelial stem cells","authors":"Mousumi Patra ,&nbsp;Ratan Sadhukhan ,&nbsp;Eva Allen,&nbsp;Faraz Kalantari,&nbsp;Heba Allam,&nbsp;Fen Xia","doi":"10.1016/j.canlet.2026.218239","DOIUrl":"10.1016/j.canlet.2026.218239","url":null,"abstract":"<div><div>Radiation-induced oral mucositis (RIOM) is a common and debilitating toxicity of radiotherapy for head and neck squamous cell carcinoma (HNSCC), often compromising treatment adherence and profoundly impairing patient quality of life. Despite its significant clinical impact, there are currently no safe and well-tolerated FDA-approved therapies to prevent or treat RIOM. The underlying mechanisms remain poorly understood but are thought to involve inflammatory responses triggered by oxidative stress and DNA damage from ionizing radiation (IR). Here, we identify SIRT2, an NAD⁺ -dependent deacetylase, as a key modulator of RIOM susceptibility. We demonstrate that both genetic and pharmacologic activation of SIRT2 robustly protects mice from developing RIOM. Mechanistically, SIRT2 enhances homologous recombination (HR)-mediated repair of DNA double-strand breaks (DSBs), thereby preserving the epithelial stem cell population of the oral mucosa and reducing mucosal injury. Importantly, SIRT2 activation—achieved via NAD⁺ supplementation in vitro or nicotinamide riboside (NR) in vivo—does not compromise the tumoricidal efficacy of IR in HNSCC models. These findings uncover a previously unrecognized protective role for SIRT2 in mucosal radiation injury and establish its activation as a promising, non-oncogenic therapeutic strategy to mitigate RIOM in patients receiving radiotherapy for head and neck cancer.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218239"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145948587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ABCG2-mediated SN-38 efflux drives resistance to Sacituzumab govitecan in urothelial carcinoma","authors":"Isabella Prantl ,&nbsp;Reinhard Grausenburger ,&nbsp;Julia Müller ,&nbsp;Oliver Baumfried ,&nbsp;Iris Elisabeth Ertl ,&nbsp;Christoph Nössing ,&nbsp;Paula Herek ,&nbsp;Christine Pirker ,&nbsp;Daniel Valcanover ,&nbsp;Yuri Bastos-Moreira ,&nbsp;Eszter Borsos ,&nbsp;Lena Marie Hauser ,&nbsp;Luis Rupp ,&nbsp;Ursula Lemberger ,&nbsp;Lisa Gabler-Pamer ,&nbsp;Ekaterina Laukhtina ,&nbsp;Agata Suleja ,&nbsp;André Oszwald ,&nbsp;Gabriel Wasinger ,&nbsp;Eva Compérat ,&nbsp;Bernhard Englinger","doi":"10.1016/j.canlet.2026.218254","DOIUrl":"10.1016/j.canlet.2026.218254","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218254"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145988201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Automated CT-derived body composition predicts pathologic response to neoadjuvant immunotherapy in non–small cell lung cancer","authors":"Yilong Huang ,&nbsp;Zhitao Wei ,&nbsp;Guanchao Ye ,&nbsp;Yanfen Cui ,&nbsp;Chuanpu Li ,&nbsp;Guangyao Wu ,&nbsp;Wei Yang ,&nbsp;Bingqian Zhang ,&nbsp;Zhenguang Zhang ,&nbsp;Yuanming Jiang ,&nbsp;Lizza E.L. Hendriks ,&nbsp;Leonard Wee ,&nbsp;Dirk De Ruysscher ,&nbsp;Andre Dekker ,&nbsp;Lei Shi ,&nbsp;Zaiyi Liu ,&nbsp;Bo He ,&nbsp;Zhenwei Shi","doi":"10.1016/j.canlet.2025.218229","DOIUrl":"10.1016/j.canlet.2025.218229","url":null,"abstract":"<div><div>Tumor-intrinsic biomarkers alone insufficiently predict pathological complete response (pCR) to neoadjuvant immunochemotherapy (NICT) in non-small cell lung cancer (NSCLC). Artificial intelligence (AI)-based three-dimensional CT-derived body composition may provide complementary predictive value. We evaluated its association with pCR following NICT in NSCLC. This multicenter retrospective study of NSCLC patients treated with NICT in China between July 2019 and July 2024. Pre- and post-treatment CT scans were used for automated T1–T12 localization and volumetric body composition segmentation. Metrics included skeletal muscle, intermuscular, visceral, and subcutaneous adipose volume index (SAVI), and their percentage changes between scans. Among 657 patients (mean age, 61.3 years; 87.4 % men), pCR rates were 39.7 % (training), 38.4 % (internal validation), and 34.9 % (external validation). In multivariable analysis, high baseline skeletal muscle volume index (SMVI) was independently associated with pCR (OR = 2.22). During NICT, each 1 % relative increase in SMVI was associated with a 16 % higher likelihood of pCR (OR = 1.16), whereas every 10 % relative increase in SAVI improved pCR probability (OR = 1.56). A machine learning model integrating clinical variables, baseline SMVI, %ΔSMVI, and %ΔSAVI demonstrated significantly better discrimination than models using clinical variables alone (<em>p</em> &lt; 0.05) in all cohorts. The performance was observed in the internal and external validation cohorts, with sensitivities of 62.1 % and 52.8 %, and specificities of 66.7 % and 74.7 %, respectively. AI-based CT–derived body composition quantification, particularly baseline SMVI and dynamic changes in SMVI and SAVI during NICT, are independently associated with pCR in NSCLC. Incorporating these modifiable biomarkers into predictive models improves performance beyond clinical variables alone.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218229"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145931644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amino acid metabolic reprogramming in clear cell renal cell carcinoma: Pathogenic mechanisms and therapeutic targeting","authors":"Junzhe Xie,&nbsp;Fangjing Ni,&nbsp;Jialiang Shao,&nbsp;Dongliang Zhang,&nbsp;Tuanjie Guo,&nbsp;Xiang Wang","doi":"10.1016/j.canlet.2026.218244","DOIUrl":"10.1016/j.canlet.2026.218244","url":null,"abstract":"<div><div>Kidney cancer is a major global health burden, with clear cell renal cell carcinoma (ccRCC) as the most common and aggressive subtype. Beyond the typical alterations of high glucose uptake and lipid accumulation, amino acid metabolism dysregulation in ccRCC is also gradually being uncovered. Pathways involving glutamine, cystine, serine, glycine, branched-chain amino acids, methionine, aspartate, arginine, proline and tryptophan are extensively rewired. These alterations enable cancer cells to sustain proliferation and biosynthesis, maintain redox balance, remodel the immune microenvironment, and develop resistance to therapy. At the same time, such reprogramming creates metabolic dependencies and vulnerabilities, including glutamine and cystine addiction as well as arginine auxotrophy. Dysregulation of key enzymes such as GLS1, ASS1 and IDO1 further highlights potential therapeutic targets. Exploiting these vulnerabilities through metabolic inhibitors or rational combinations with targeted and immunotherapy holds promise for overcoming resistance and improving outcomes in ccRCC.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218244"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145910580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Price transparency compliance and variation for proton therapy in the United States","authors":"Kasey R. Cargill ,&nbsp;Noah M. Feder ,&nbsp;Tyler Wilhite ,&nbsp;Walid F. Gellad ,&nbsp;Heath D. Skinner ,&nbsp;Yvonne M. Mowery ,&nbsp;Christopher T. Wilke","doi":"10.1016/j.canlet.2026.218260","DOIUrl":"10.1016/j.canlet.2026.218260","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"640 ","pages":"Article 218260"},"PeriodicalIF":10.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}