Cancer letters最新文献

{"title":"Cervical Cancer Incidence and Mortality Trends in China: The Role of Screening","authors":"Meiwen Yuan ,&nbsp;Yuting Hong ,&nbsp;Yushu Feng ,&nbsp;Jiaqi Sun ,&nbsp;Xuelian Zhao ,&nbsp;Shangying Hu ,&nbsp;Fanghui Zhao","doi":"10.1016/j.canlet.2026.218286","DOIUrl":"10.1016/j.canlet.2026.218286","url":null,"abstract":"<div><div>In China, cervical cancer incidence and mortality have continued to increase despite more than 15 years of nationwide organized screening, raising questions about the population-level impact of screening. Using national cancer registry data from 2004 to 2018, we analyzed temporal trends in age-standardized incidence rates (ASIRs) and mortality rates (ASMRs), as well as age-specific rates, using Joinpoint regression, and assessed their correlations with age-specific screening coverage.</div><div>From 2004 to 2018, ASIR increased from 6.06 to 11.81 per 100,000, but the annual growth rate slowed markedly after 2007, declining from 12.5 % (95 % CI: 9.7 ∼ 15.5 %) to 3.1 % (95 % CI: 2.7 ∼ 3.4 %). Among women aged 35–44 years, incidence trends shifted from a sharp rise to a sustained decline. By contrast, ASMR rose steadily from 2.07 to 3.44 per 100,000, with an average annual increase of 4.1 % (95 % CI: 3.4 ∼ 4.8 %). Notably, mortality stabilized after a rapid early rise among women aged 40–44 years, the group with the highest screening coverage. Correlation analysis revealed strong positive associations between higher screening coverage and the deceleration of incidence (ρ = 0.85, p &lt; 0.001) and mortality trends (ρ = 0.69, p = 0.014).</div><div>These findings suggest that increased screening coverage may already be moderating incidence and mortality trends in specific age groups, particularly women aged 35–44 years. However, nationwide declines have yet to emerge, especially in rural populations where screening coverage remains low and disease burden is high. Expanding access and improving screening quality are critical to accelerate progress toward cervical cancer control in China.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218286"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146084430","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":"Ganoderma lucidum polysaccharide ameliorates cancer cachexia with enhanced efficacy in aged group by reprogramming arginine metabolism to modulate Treg formation","authors":"Chunmiao Deng ,&nbsp;Yunfang Chen ,&nbsp;Jiaojiao Xu ,&nbsp;Chanjin Liang ,&nbsp;Cui Shao ,&nbsp;Shiqi Mei ,&nbsp;Yongkang Xu ,&nbsp;Yin Li ,&nbsp;Cancan Zheng ,&nbsp;Yichang Luo ,&nbsp;Xingyuan Shi","doi":"10.1016/j.canlet.2026.218247","DOIUrl":"10.1016/j.canlet.2026.218247","url":null,"abstract":"<div><div>Cancer cachexia is a syndrome characterized by profound weight loss, muscle wasting, and metabolic disturbance in cancer patients. Cancer-associated cachexia represents significant biological and clinical challenges that profoundly affect human health. Approximately 20 % of cancer patients succumb directly to cachexia-related complications. Aging is characterized by a gradual decline in physiological functions and an increased vulnerability to chronic diseases. However, whether aging inherently increases vulnerability to cachexia or exacerbates its progression remains unclear, impeding the development of targeted strategies for this high-risk population. <em>Ganoderma lucidum</em> polysaccharides (GLP) have demonstrated diverse pharmacological activities; however, their potential role in attenuating of tumor cachexia remains inadequately explored and warrants further investigation. In this study, GLP was found to mitigate tumor cachexia <em>in vitro</em> and <em>in vivo</em> models, as evidenced by rescuing significant weight loss, muscle atrophy, and adipose tissue breakdown. Notably, its therapeutic potency is more profoundly marked in aged mice than in young ones. Mechanistically, GLP alleviated myofiber atrophy and dyslipolysis by inactivating NF-κB and AMPK pathways, while also activating Treg cells by regulating arginine metabolism. In conclusion, our findings indicate that GLP exhibits cachexia-attenuating activities, thereby positioning it as a potential therapeutic candidate for aging-related conditions.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218247"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145942582","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":"High-throughput drug screening for targeting polyploid cancer cells with an interactive web portal","authors":"Hsiao-Chun Chen ,&nbsp;Li-Ju Wang ,&nbsp;Chien-Hung Shih ,&nbsp;Huikang Ye ,&nbsp;Ying-Ju Lai ,&nbsp;Jinxiong Cheng ,&nbsp;Yuan Zhang ,&nbsp;Yushu Ma ,&nbsp;Tiffany Habib ,&nbsp;Shailrajsinh H. Jhala ,&nbsp;Hsi-Chun Wang ,&nbsp;Yu-Chiao Chiu ,&nbsp;Yu-Chih Chen","doi":"10.1016/j.canlet.2026.218289","DOIUrl":"10.1016/j.canlet.2026.218289","url":null,"abstract":"","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218289"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146117453","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":"Targeting ATR signaling in sarcoma with homologous recombination deficiency","authors":"L. Planas-Paz ,&nbsp;M. Zehnder ,&nbsp;N. Desboeufs ,&nbsp;S. Kollar ,&nbsp;Y. Chen ,&nbsp;S. Schneebeli ,&nbsp;R. Schenk ,&nbsp;M.P. Schmid ,&nbsp;M. Lopes ,&nbsp;A. Weber ,&nbsp;C. Pauli","doi":"10.1016/j.canlet.2026.218300","DOIUrl":"10.1016/j.canlet.2026.218300","url":null,"abstract":"<div><div>Homologous recombination deficiency (HRD) has emerged as a key vulnerability in selected cancer types and is associated with response to platinum and PARPi-based treatment strategies. However, additional biomarkers and targeted therapy options are needed to broaden the range of patients that could benefit from this therapeutic niche. Here, we show that the SARC-HRD signature, composed of ten genes of the homologous recombination repair pathway, stratifies a cohort of sarcoma patients, and associates with genomic biomarkers of HRD, with disease progression and with the CINSARC prognostic signature. Equivalently to CINSARC, high levels of SARC-HRD are associated with poor metastasis-free survival, underscoring the potential of SARC-HRD to predict disease outcome. By pharmacotyping patient-derived cell models, we identified promising drug targets within the DNA damage response (DDR) for sarcoma with HRD traits. Inhibition of ATR, CHK1 and WEE1 elicited synthetic lethality in sarcoma cells with HRD, which concomitantly showed an upregulation of ATR signaling. Combinatorial drug testing further revealed synergistic drug combinations between ATRi, WEE1i, PARP1/2i and chemotherapeutic agents with potential clinical impact. Mechanistically, targeting ATR signaling at multiple levels induced a replication defect, mitotic abnormalities and apoptotic cell death. Taken together, our results demonstrate the therapeutic benefit of targeting DDR mechanisms in sarcoma with HRDness traits and their potential clinical utility for treating a broader spectrum of tumor types.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218300"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130603","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":"Dysregulation of the ALDH1A3/PML–RARα axis promotes the progression of acute promyelocytic leukemia","authors":"Jiao Cai ,&nbsp;Cheng-Hui Liang ,&nbsp;Li-Ping Han ,&nbsp;Hong-Ying Jiang ,&nbsp;Jiang-Jie Duan ,&nbsp;Fu Li ,&nbsp;Jia Liu ,&nbsp;Cai Liang ,&nbsp;Lei Gao ,&nbsp;Shi-Cang Yu","doi":"10.1016/j.canlet.2026.218280","DOIUrl":"10.1016/j.canlet.2026.218280","url":null,"abstract":"<div><div>Dysfunction of the retinoic acid (RA) signaling pathway, which is mediated by the formation of the <em>PML–RARA</em> fusion gene, plays a central role in the pathogenesis of acute promyelocytic leukemia (APL). The activation of this pathway depends on the binding of the ligand RA to RA receptors (RARs). Members of aldehyde dehydrogenase (ALDH) family are key enzymes responsible for the biosynthesis of endogenous RA and are highly enriched in various cancer stem cell subpopulations; however, their specific contributions to APL pathogenesis remain poorly understood. In this study, we demonstrate that the expression of aldehyde dehydrogenase family member 1A3 (ALDH1A3) is negatively correlated with APL progression. Through DNA pull-down assays, liquid chromatography-tandem mass spectrometry (LC‒MS/MS) analysis, chromatin immunoprecipitation (ChIP), dual-luciferase reporter assays and electrophoretic mobility shift assay (EMSA), we show that ALDH1A3 cooperates with the transcription factor Myc-associated zinc finger protein (MAZ) to transcriptionally repress PML–RARα expression. Furthermore, EMSA and methylated DNA immunoprecipitation (MeDIP) analyses reveal that PML–RARα increases methylation of the <em>ALDH1A3</em> promoter, thereby suppressing its expression in APL patients. This reciprocal inhibitory relationship is correlated with clinical remission in APL. Integrated RNA sequencing (RNA-seq) and Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) analyses indicate that ALDH1A3 overexpression is associated with increased chromatin accessibility and the upregulation of genes involved in cellular differentiation. Notably, demethylation therapy induced sustained complete remission in patients with refractory and recurrent APL during experimental treatment. Our findings underscore the critical role of ALDH1A3 in leukemogenesis and highlight its potential as a therapeutic target in APL.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218280"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043574","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":"Succinate dehydrogenase B palmitoylation promotes T cell exhaustion through the H3K27ac-PD1 axis in pancreatic cancer","authors":"Fuxin Huang ,&nbsp;Cheukfai Li ,&nbsp;Yue Chen ,&nbsp;Jianmin Lu ,&nbsp;Jike Fang ,&nbsp;Zhongyan Zhang ,&nbsp;Jinhui Wei ,&nbsp;Chuanzhao Zhang ,&nbsp;Baohua Hou ,&nbsp;Shanzhou Huang","doi":"10.1016/j.canlet.2026.218277","DOIUrl":"10.1016/j.canlet.2026.218277","url":null,"abstract":"<div><div>Palmitoyltransferase ZDHHC5 (DHHC5) is a palmitoylation regulator that adds palmitate to various protein substrates. Its role in pancreatic cancer (PC) remains unclear, thus posing significant challenges to the promotion of the “cold tumor” immune microenvironment, the development of new drugs, and targeted therapy. In this study, through comprehensive bioinformatics analysis, we determined the association between DHHC5 and various immune and metabolic components which we refer to as post-translational modification checkpoint of palmitoylation (Palm-PTM-checkpoint). We found that in pancreatic cancer, DHHC5 upregulates the palmitoylation of succinate dehydrogenase B (SDHB), stabilizes the SDHB protein, inhibits lysosomal degradation, and increases fumarate production by promoting succinate dehydrogenase activity. This process suppresses the overall immune microenvironment, especially the anti-tumor immunity of T cells. Mechanistically, the excessive fumarate produced by the palmitoylation cycle of SDHB in cancer cells increases the production of acetyl-CoA in T cells and promotes T-cell exhaustion by upregulating the H3K27 acetylation (H3K27ac) -PD1 axis. Additionally, based on the sequence near the palmitoylation site of SDHB, we designed an intracellular penetrating peptide CPP-S1 targeting SDHB palmitoylation. As a competitive inhibitor, CPP-S1 inhibits the palmitoylation modification of SDHB, reduces the SDHB protein level, and suppresses the tumor growth of pancreatic cancer cells, with enhanced effects when used in combination with anti-PD1 therapy. These findings reveal a new strategy to overcome the immune escape mediated by the DHHC5-SDHB axis in pancreatic cancer immunotherapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218277"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040283","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":"Changing landscape in stage, treatment and survival of gastric cancer in China 1998–2022: Insights of 40,158 patients from the National Gastric Cancer Cohort","authors":"Lulu Zhao ,&nbsp;Zhihao Chen ,&nbsp;Fan Zhang ,&nbsp;Fengzhu Zhang ,&nbsp;Xianchun Gao ,&nbsp;Xiang Wang ,&nbsp;Xiadong Zhou ,&nbsp;Shun Zhang ,&nbsp;Xue Han ,&nbsp;Zerong Wang ,&nbsp;Xiaoyi Luan ,&nbsp;Penghui Niu ,&nbsp;Wanqing Wang ,&nbsp;Zhiming Fu ,&nbsp;Huang Huang ,&nbsp;Ranran Qie ,&nbsp;Weili Han ,&nbsp;Rong Zheng ,&nbsp;Ling Chen ,&nbsp;Likun Qi ,&nbsp;Yingtai Chen","doi":"10.1016/j.canlet.2026.218261","DOIUrl":"10.1016/j.canlet.2026.218261","url":null,"abstract":"<div><h3>Introduction</h3><div>Assessing progress in cancer control at the national level is crucial, as it offers key insights into the overall effectiveness of the health system. Here, we aimed to describe 20-year trends in stage distribution, treatment patterns, and survival for gastric cancer in China, and to estimate stage- and treatment-specific 1-, 3-, 5-, and 10-year overall survival (OS) at the national level.</div></div><div><h3>Methods</h3><div>In this study, we included data from 40,158 patients diagnosed with gastric cancer between 1998 and 2022, derived from nine tertiary grade-A hospitals located across all four major regions of China. The characteristics, treatment modalities, and survival outcomes were analyzed across four predefined time periods: period 1 (1998–2005), period 2 (2006–2010), period 3 (2011–2015), and period 4 (2016–2022). Stage- and treatment-specific survival with 95 % confidence intervals (CIs) was estimated using the Kaplan–Meier method; differences were assessed by log-rank test.</div></div><div><h3>Results</h3><div>During the study period, there was an increasing proportion of patients with early stage gastric cancer from 9.8 % in 1998 to 19.5 % in 2022, while patients with metastatic disease remained stable. For early gastric cancer classified as cT1aN0, the proportion of patients undergoing endoscopic resection increased from 0.0 % in period 1–30.4 % in period 4. Among patients with locally advanced gastric cancer, the proportion receiving neoadjuvant therapy increased from 0.8 % to 17.3 %. Regarding survival outcomes, the 5-year OS rate of gastric cancer cohort increased from 38.2 % in period 1–46.1 % in period 4. Stage-specific 5-year OS rates were 90.0 % (stage I), 69.0 % (stage II), 37.0 % (stage III), and 13.7 % (stage IV). Compared with Japan, gastric cancer patients with stage IA in China exhibited higher 5-year OS rate (91.9 % vs. 89.6 %) but a much lower proportion (16.9 % vs. 43.6 %). Survival for stage IIIA–IIIC was poorer in China (48.5 % vs. 59.3 %, 34.7 % vs. 45.6 %, 21.8 % vs. 29.9 %; respectively).</div></div><div><h3>Conclusions</h3><div>From 1998 to 2022, the proportion of patients diagnosed with early-stage gastric cancer in China gradually increased, and treatment strategies changed substantially over time, accompanied by a modest improvement in the 5-year OS rate. The disparities in stage distribution and survival outcomes between China and Japan highlight the need to further improve early detection of gastric cancer and to develop more effective treatment modalities for patients with stage III disease in China.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218261"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146046114","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":"Acute myocardial infarction following allogeneic hematopoietic stem cell transplantation: A national cohort study","authors":"Peng Zhao ,&nbsp;Zhi-Xue Li ,&nbsp;Er-Lie Jiang ,&nbsp;Sheng-Jin Fan ,&nbsp;Dai-Hong Liu ,&nbsp;Peng-Cheng He ,&nbsp;Jin-Song Yan ,&nbsp;Ming Jiang ,&nbsp;Ya-Jing Xu ,&nbsp;Ling-Hui Xia ,&nbsp;Jin-Hai Ren ,&nbsp;Hong-Yu Zhang ,&nbsp;Yu-Jun Dong ,&nbsp;Wei-Da Wang ,&nbsp;Yang Liang ,&nbsp;Hai-Xia Fu ,&nbsp;Qiu-Sha Huang ,&nbsp;Jin Wu ,&nbsp;Zhuo-Yu An ,&nbsp;Yue Jin ,&nbsp;Xiao-Hui Zhang","doi":"10.1016/j.canlet.2026.218287","DOIUrl":"10.1016/j.canlet.2026.218287","url":null,"abstract":"<div><div>Acute myocardial infarction (MI) is a relatively rare but life-threatening complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Information regarding the clinical characteristics, outcomes, and prognostication of post-transplant MI is lacking. We conducted a nationally representative cohort study at 34 centers in China. Patients with MI were retrospectively identified among those who underwent allo-HSCT. The diagnosis and classification of MI were reviewed according to established guidelines. One hundred thirteen patients were analyzed, including 23 patients with T1MI, 87 patients with T2MI, and three patients with T3MI. Patients with T2MI had a significantly higher mortality rate. Thrombotic microangiopathy (TMA) frequently coexisted with T2MI and adversely affected the overall survival. Disease relapse or progression, a platelet count &lt;20 × 10⁹/L, active TMA at MI onset, and Killip class 3–4 were identified as independent risk factors for 2-month mortality. We divided these patients into a low-risk group (without risk factors), an intermediate-risk group (1–2 risk factors), and a high-risk group (3–4 risk factors). Significantly different 2-month mortality rates were observed across these groups (11.1 %, 59.3 %, and 100.0 %, respectively). Available angiographic imaging data and antiplatelet therapy after MI onset may be associated with improved outcome, but the survival benefits and optimized medication use in patients with post-transplant MI require further validation. These findings may facilitate refined monitoring and management strategies of MI in the post-transplant population.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218287"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146103908","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":"MEOX2 enhances DNA repair and therapy resistance in Glioblastoma stem-like cells via PARP1 interaction","authors":"Monia Russo ,&nbsp;Elvia Valentini ,&nbsp;Vincenza Aliperti ,&nbsp;Federico Copparoni ,&nbsp;Amanda Linkous ,&nbsp;Claudia Montaldo ,&nbsp;Silvia Soddu ,&nbsp;Jean-Maxime Besson ,&nbsp;Marie Lopez ,&nbsp;Manuela Helmer Citterich ,&nbsp;Alessandro Michienzi ,&nbsp;Marco Tripodi ,&nbsp;Silvia Anna Ciafrè ,&nbsp;Silvia Galardi","doi":"10.1016/j.canlet.2026.218284","DOIUrl":"10.1016/j.canlet.2026.218284","url":null,"abstract":"<div><div>The most widely accepted hypothesis for glioblastoma development posits that glioblastoma stem-like cells (GSCs) play a central role in tumor initiation, recurrence, and resistance to both chemotherapy and radiotherapy. We and others previously showed the importance of Mesenchyme Homeobox 2 (MEOX2) in supporting GSC survival and metabolism. In the present work, we demonstrate that MEOX2 also promotes DNA damage repair and contributes to resistance against genotoxic therapies in GSCs. Using a GLICO (GLioblastoma Cerebral Organoid) model, we show that MEOX2 knockdown impairs tumor growth and increases sensitivity to temozolomide (TMZ). Mechanistically, we find that MEOX2 depletion in 2D culture systems compromises genomic stability and impairs DNA repair. Co-immunoprecipitation and mass spectrometry analyses identified poly ADP-ribose polymerase 1 (PARP1) as a novel MEOX2 interactor. Consistent with this, MEOX2-depleted cells exhibit reduced PARylation levels and increased sensitivity to the PARP1 inhibitor Talazoparib, highlighting a potential therapeutic vulnerability.</div><div>Altogether, our findings reveal a previously unrecognized role for MEOX2 in the DNA damage response of GSCs, particularly in promoting survival and recovery after chemotherapy and ionizing radiation. These results also suggest that MEOX2 functions as a partner of PARP1 and may represent a promising therapeutic target in GBM.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218284"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146090229","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":"The role of the microbiota in cancer drug resistance and emerging therapeutic strategies","authors":"Chang Che ,&nbsp;Yelu Zhou ,&nbsp;Liyu Chen ,&nbsp;Sifan Li,&nbsp;Daiming Fan,&nbsp;Yuanyuan Lu,&nbsp;Xiaodi Zhao","doi":"10.1016/j.canlet.2026.218305","DOIUrl":"10.1016/j.canlet.2026.218305","url":null,"abstract":"<div><div>Drug resistance remains a significant obstacle in cancer therapy, severely compromising therapeutic efficacy and patient survival outcomes. Targeted therapy is now a central strategy for cancers with defined molecular abnormalities, employing agents that interact with specific genetic or molecular targets. Immunotherapy has emerged as a transformative approach in oncology by enhancing the immune system's ability to identify and eradicate cancer cells. Although microbial communities are increasingly acknowledged for their involvement in tumorigenesis and metastasis, their impact on drug resistance, including resistance to chemotherapy, immunotherapy, and targeted therapy, remains insufficiently investigated. Clinical evidence further reveals significant correlations between microbiota composition and survival outcomes, such as progression-free survival and recurrence rates. Microbiota contribute to resistance through complex mechanisms. Pathogenic bacteria can impair chemotherapy by degrading drugs and suppressing immune responses, whereas certain beneficial bacteria may enhance immunity and modulate metabolism. Notably, intratumoral microbiota directly modulate chemoresistance development through localized actions within the tumor microenvironment. This review synthesizes clinical data and mechanistic studies to delineate microbial-drug interactions, emphasizing how pathogens drive resistance through multifactorial pathways while probiotics mitigate treatment toxicity and restore drug sensitivity. We further propose novel therapeutic strategies leveraging microbe-drug interplay to overcome resistance and alleviate chemotherapy side effects, offering new approaches to enhance the efficacy of immunotherapy and targeted therapy. These findings advance the understanding of microbial contributions to drug resistance and provide new directions for clinical application in precision cancer therapy.</div></div>","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":"642 ","pages":"Article 218305"},"PeriodicalIF":10.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149248","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}