Cancer letters最新文献

TFAP2C-DDR1 axis regulates resistance to CDK4/6 inhibitor in breast cancer. TFAP2C-DDR1轴调节乳腺癌对CDK4/6抑制剂的耐药性

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-01 Epub Date: 2024-11-26 DOI: 10.1016/j.canlet.2024.217356

Muhammad Jameel Mughal, Yi Zhang, Zhuqing Li, Shuyan Zhou, Changmin Peng, Ya-Qin Zhang, Edward Seto, Min Shen, Matthew D Hall, Wenge Zhu

{"title":"TFAP2C-DDR1 axis regulates resistance to CDK4/6 inhibitor in breast cancer.","authors":"Muhammad Jameel Mughal, Yi Zhang, Zhuqing Li, Shuyan Zhou, Changmin Peng, Ya-Qin Zhang, Edward Seto, Min Shen, Matthew D Hall, Wenge Zhu","doi":"10.1016/j.canlet.2024.217356","DOIUrl":"10.1016/j.canlet.2024.217356","url":null,"abstract":"Breast cancer is the predominant malignancy with the majority of cases are characterized as HR+/HER2-subtype. Although cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have shown remarkable efficacy in treating this subtype when combined with endocrine therapy, the development of resistance to these inhibitors remains a significant clinical obstacle. Hence, there is an urgent need to explore innovative therapies and decipher the underlying mechanisms of resistance to CDK4/6i. In this study, we employed quantitative high-throughput combination screening (qHTCS) and genomics/proteomics approaches to uncover the molecular mechanisms driving resistance to CDK4/6i (palbociclib) in breast cancer. The comprehensive analyses revealed DDR1 as a potential factor implicated in mediating resistance to CDK4/6i. Specifically, DDR1 inhibition in combination with palbociclib exhibited remarkable synergistic effects, reducing cell survival signaling and promoting apoptosis in resistant cells. In-vivo xenograft model further validated the synergistic effects, showing a significant reduction in the resistant tumor growth. Exploration into DDR1 activation uncovered TFAP2C as a key transcription factor regulating DDR1 expression in palbociclib resistant cells and inhibition of TFAP2C re-sensitized resistant cells to palbociclib. Gene set enrichment analysis (GSEA) in the NeoPalAna trial demonstrated a significant enrichment of the TFAP2C-DDR1 gene set from patitens after palbociclib treatment, suggesting the possible activation of the TFAP2C-DDR1 axis following palbociclib exposure. Overall, this study provides crucial insights into the novel molecular landscape of palbociclib resistance in breast cancer, suggesting TFAP2C-DDR1 axis inhibition as a promising strategy to overcome resistance.","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217356"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738490","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}

引用次数: 0

Corrigendum to "SERPINE2/PN-1 regulates the DNA damage response and radioresistance by activating ATM in lung cancer" [Cancer Lett. 524 (2022) 268-283]. 更正："SERPINE2/PN-1通过激活肺癌中的ATM调节DNA损伤反应和放射抗性" [Cancer Lett.

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-01 Epub Date: 2024-11-24 DOI: 10.1016/j.canlet.2024.217337

Jingjing Zhang, Qiong Wu, Lucheng Zhu, Shujun Xie, Linglan Tu, Yuhong Yang, Kan Wu, Yanyan Zhao, Yuqing Wang, Yasi Xu, Xueqin Chen, Shenglin Ma, Shirong Zhang

引用次数: 0

Corrigendum to "Precision meets repurposing: Innovative approaches in human papillomavirus and Epstein-Barr virus-driven cancer therapy" [Cancer Lett. 607 (2024) 217318].

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-01 Epub Date: 2024-11-30 DOI: 10.1016/j.canlet.2024.217358

Queenie Fernandes

引用次数: 0

Corrigendum to "NSUN4 mediated RNA 5-methylcytosine promotes the malignant progression of glioma through improving the CDC42 mRNA stabilization" [Cancer Lett. (2024) 597 217059].

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-01 Epub Date: 2024-11-30 DOI: 10.1016/j.canlet.2024.217351

Zhen Zhao, Yujie Zhou, Peng Lv, Ting Zhou, Hanyuan Liu, Youxi Xie, Zhipeng Wu, Xuan Wang, Hongyang Zhao, Jianglin Zheng, Xiaobing Jiang

引用次数: 0

Frontiers in pancreatic cancer on biomarkers, microenvironment, and immunotherapy. 胰腺癌的生物标志物、微环境和免疫疗法前沿。

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-01 Epub Date: 2024-11-22 DOI: 10.1016/j.canlet.2024.217350

Baofa Yu, Shengwen Shao, Wenxue Ma

{"title":"Frontiers in pancreatic cancer on biomarkers, microenvironment, and immunotherapy.","authors":"Baofa Yu, Shengwen Shao, Wenxue Ma","doi":"10.1016/j.canlet.2024.217350","DOIUrl":"10.1016/j.canlet.2024.217350","url":null,"abstract":"Pancreatic cancer remains one of the most challenging malignancies to treat due to its late-stage diagnosis, aggressive progression, and high resistance to existing therapies. This review examines the latest advancements in early detection, and therapeutic strategies, with a focus on emerging biomarkers, tumor microenvironment (TME) modulation, and the integration of artificial intelligence (AI) in data analysis. We highlight promising biomarkers, including microRNAs (miRNAs) and circulating tumor DNA (ctDNA), that offer enhanced sensitivity and specificity for early-stage diagnosis when combined with multi-omics panels. A detailed analysis of the TME reveals how components such as cancer-associated fibroblasts (CAFs), immune cells, and the extracellular matrix (ECM) contribute to therapy resistance by creating immunosuppressive barriers. We also discuss therapeutic interventions that target these TME components, aiming to improve drug delivery and overcome immune evasion. Furthermore, AI-driven analyses are explored for their potential to interpret complex multi-omics data, enabling personalized treatment strategies and real-time monitoring of treatment response. We conclude by identifying key areas for future research, including the clinical validation of biomarkers, regulatory frameworks for AI applications, and equitable access to innovative therapies. This comprehensive approach underscores the need for integrated, personalized strategies to improve outcomes in pancreatic cancer.","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217350"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709208","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}

引用次数: 0

Chemoresistance-motility signature of molecular evolution to chemotherapy in non-muscle-invasive bladder cancer and its clinical implications.

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-01 Epub Date: 2024-11-26 DOI: 10.1016/j.canlet.2024.217339

Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem

{"title":"Chemoresistance-motility signature of molecular evolution to chemotherapy in non-muscle-invasive bladder cancer and its clinical implications.","authors":"Mi-So Jeong, Seung-Woo Baek, Gi-Eun Yang, Jeong-Yeon Mun, Jeong Ah Kim, Tae-Nam Kim, Jong-Kil Nam, Yung-Hyun Choi, Ju-Seog Lee, In-Sun Chu, Sun-Hee Leem","doi":"10.1016/j.canlet.2024.217339","DOIUrl":"10.1016/j.canlet.2024.217339","url":null,"abstract":"Non-muscle-invasive bladder cancer (NMIBC) often recurs and can progress to MIBC due to resistance to treatments like intravesical chemotherapy or Bacillus Calmette-Guérin (BCG). Therefore, we established the Gemcitabine-Resistant Cells (GRCs) to study the molecular evolution under external pressure. A 63-gene Chemoresistance-Motility (CrM) signature was created to identify stage-specific traits of GRCs. This signature was tested on 1846 samples using log-rank tests and Cox regression to evaluate clinical utility. Early and intermediate resistance stages showed increased cell motility and metastatic potential. FAK, PI3K-AKT, and TGFβ pathways were activated first, followed by MAPK signaling. Single-cell analysis and experiments utilizing the CrM signature confirmed interaction with cancer-associated fibroblasts (CAFs). The high-CrM groups mainly included NMIBC patients with poor prognosis (progression-free survival analysis by log-rank test based on UROMOL cohort, p < 0.001), T1-high grade, high European Association of Urology (EAU) risk score, and also included MIBC patients with a history of metastases. Additionally, relative ineffectiveness was observed for BCG (the chi-square test based on BRS cohort, p = 0.02) and immune checkpoint inhibitors (ICIs) in patients with high-CrM. In addition, we identified five drugs that can be used with gemcitabine in these patients, including doxorubicin, docetaxel, paclitaxel, napabucacin, and valrubicin, and verified their efficacy. This study provides insights into NMIBC progression to MIBC via molecular evolution. The CrM signature can assess NMIBC prognosis and BCG treatment response, suggesting alternative treatments. Furthermore, these results need to be prospectively validated.","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217339"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749568","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}

引用次数: 0

Advancements and challenges of R-loops in cancers: Biological insights and future directions.

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-01 Epub Date: 2024-11-27 DOI: 10.1016/j.canlet.2024.217359

Dengxiong Li, Fanglin Shao, Xinrui Li, Qingxin Yu, Ruicheng Wu, Jie Wang, Zhipeng Wang, Dilinaer Wusiman, Luxia Ye, Yiqing Guo, Zhouting Tuo, Wuran Wei, Koo Han Yoo, William C Cho, Dechao Feng

{"title":"Advancements and challenges of R-loops in cancers: Biological insights and future directions.","authors":"Dengxiong Li, Fanglin Shao, Xinrui Li, Qingxin Yu, Ruicheng Wu, Jie Wang, Zhipeng Wang, Dilinaer Wusiman, Luxia Ye, Yiqing Guo, Zhouting Tuo, Wuran Wei, Koo Han Yoo, William C Cho, Dechao Feng","doi":"10.1016/j.canlet.2024.217359","DOIUrl":"10.1016/j.canlet.2024.217359","url":null,"abstract":"R-loops involve in various biological processes under human normal physiological conditions. Disruption of R-loops can lead to disease onset and affect the progression of illnesses, particularly in cancers. Herein, we summarized and discussed the regulative networks, phenotypes and future directions of R-loops in cancers. In this review, we highlighted the following insights: (1) R-loops significantly influence cancer development, progression and treatment efficiency by regulating key genes, such as PARPs, BRCA1/2, sex hormone receptors, DHX9, and TOP1. (2) Currently, the ATM, ATR, cGAS/STING, and noncanonical pathways are the main pathways that involve in the regulatory network of R-loops in cancer. (3) Cancer biology can be modulated by R-loops-regulated phenotypes, including RNA methylation, DNA and histone methylation, oxidative stress, immune and inflammation regulation, and senescence. (4) Regulation of R-loops induces kinds of drug resistance in various cancers, suggesting that targeting R-loops maybe a promising way to overcome treatment resistance. (5) The role of R-loops in tumorigenesis remains controversial, and senescence may be a crucial research direction to unravel the mechanism of R-loop-induced tumorigenesis. Looking forward, further studies are needed to elucidate the specific mechanisms of R-loops in cancer, laying the groundwork for preclinical and clinical research.","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217359"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142754793","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}

引用次数: 0

HSP90 inhibitor AUY922 suppresses tumor growth and modulates immune response through YAP1-TEAD pathway inhibition in gastric cancer. HSP90抑制剂AUY922通过抑制YAP-TEAD通路抑制胃癌患者的肿瘤生长并调节免疫反应

IF 9.1 1区医学

Cancer letters Pub Date : 2025-02-01 Epub Date: 2024-11-26 DOI: 10.1016/j.canlet.2024.217354

Katsuhiro Yoshimura, Gengyi Zou, Yibo Fan, Kohei Yamashita, Lingzhi Wang, Jingjing Wu, Ruiping Wang, Shan Shao, Ailing W Scott, Jiankang Jin, Melissa Pool Pizzi, Xiaodan Yao, Calena-Abel Brown, Linghua Wang, Qiong Gan, Rebecca E Waters, Feng Yin, Shumei Song, Shilpa S Dhar, Jaffer A Ajani

{"title":"HSP90 inhibitor AUY922 suppresses tumor growth and modulates immune response through YAP1-TEAD pathway inhibition in gastric cancer.","authors":"Katsuhiro Yoshimura, Gengyi Zou, Yibo Fan, Kohei Yamashita, Lingzhi Wang, Jingjing Wu, Ruiping Wang, Shan Shao, Ailing W Scott, Jiankang Jin, Melissa Pool Pizzi, Xiaodan Yao, Calena-Abel Brown, Linghua Wang, Qiong Gan, Rebecca E Waters, Feng Yin, Shumei Song, Shilpa S Dhar, Jaffer A Ajani","doi":"10.1016/j.canlet.2024.217354","DOIUrl":"10.1016/j.canlet.2024.217354","url":null,"abstract":"Heat shock protein 90 (HSP90), a vital chaperone involved in the folding and stabilization of various cellular proteins, regulates key functions in many tumor cells. In the context of gastric adenocarcinoma (GAC), where HSP90's role remains largely unexplored, we aimed to investigate the significance of HSP90 inhibitor, AUY922, in regulating the YAP1/TEAD pathway and its association with the tumor immune microenvironment (TME). Our results showed that AUY922 effectively inhibited GAC aggressiveness in both the invitro and invivo models, induced apoptosis, and cell-cycle arrest. Various functional assays elucidated that AUY922 potently inhibited the expression and interaction among YAP1/TEAD and HSP90, resulting in down-regulation of target functional genes. AUY922 additionally altered the tumor microenvironment (TME) into an inflamed state with increased cytokine production in T cells, including interferon gamma, granzyme B, and perforin, and inhibited M2 polarization of tumor-associated macrophages, rendering it a favorable partner for immune checkpoint inhibition. Our findings highlighted the suggestion of targeting HSP90 in GAC therapy via down-regulating YAP1/TEAD signaling. Additionally, our results suggest that AUY922's ability to reshape the GAC TME favoring the host sets the stage for a clinical trial that combines HSP90 and checkpoint inhibition, where HSP90 could serve as a biomarker for patient selection.","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217354"},"PeriodicalIF":9.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738523","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}

引用次数: 0

Tumor-derived CCL15 regulates RNA m⁶A methylation in cancer-associated fibroblasts to promote hepatocellular carcinoma growth.

IF 9.1 1区医学

Cancer letters Pub Date : 2024-12-27 DOI: 10.1016/j.canlet.2024.217420

Chaomin Wang, Dong Dong, Na Zhao, Yang Liu, Changsen Bai, Jialei Hua, Ranliang Cui, Xi Wei, Ting Zhao, Ning Ji, Shuaini Yang, Jie Zhao, Huikai Li, Yueguo Li

{"title":"Tumor-derived CCL15 regulates RNA m6A methylation in cancer-associated fibroblasts to promote hepatocellular carcinoma growth.","authors":"Chaomin Wang, Dong Dong, Na Zhao, Yang Liu, Changsen Bai, Jialei Hua, Ranliang Cui, Xi Wei, Ting Zhao, Ning Ji, Shuaini Yang, Jie Zhao, Huikai Li, Yueguo Li","doi":"10.1016/j.canlet.2024.217420","DOIUrl":"https://doi.org/10.1016/j.canlet.2024.217420","url":null,"abstract":"Hepatocellular carcinoma (HCC) is a lethal malignancy characterized by rapid growth. The interaction between tumor cells and cancer-associated fibroblasts (CAFs) significantly influences HCC progression. CCL15, a CC chemokine family member, is predominantly expressed in HCC and strongly correlates with tumor size, indicating its critical role in HCC growth. However, previous studies suggest that CCL15 does not directly stimulate cancer cell proliferation. The specific role and mechanism of CCL15 in HCC proliferation remain unknown. Here, we identified that CCL15 was predominantly overexpressed by HCC cells through single-cell RNA sequencing data and immunofluorescence. We discovered that CCL15 promotes HCC growth by stimulating the crosstalk between HCC cells and CAFs via CCR1 signaling, as evidenced by co-culture assays, organoid models, and allograft models. Mechanistically, CCL15 induced the expression of FTO in CAFs through the STAT3 pathway. By m6A sequencing and RNA sequencing, we found that CEBPA mRNA, a transcription factor regulating CXCL5 expression, was a target of FTO. CXCL5, secreted by CAFs, activated the CXCR2 receptor on HCC cells and enhanced their proliferation. Notably, we found that interfering with CCL15 signaling using a neutralizing antibody attenuated HCC growth in heterotypic co-injection and patient-derived xenograft murine models. Finally, CXCL5 also upregulated CCL15 expression in HCC cells by modulating P53 expression through MDM2, forming a positive feedback loop. Our study unveiled CCL15 as a key mediator in HCC progression, facilitating communication between HCC cells and CAFs. This highlights a novel regulatory axis in HCC and suggests that targeting CCL15 could be a potential therapeutic strategy.","PeriodicalId":9506,"journal":{"name":"Cancer letters","volume":" ","pages":"217420"},"PeriodicalIF":9.1,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142902604","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}

引用次数: 0

Corrigendum to "Cellular dynamics of tumor microenvironment driving immunotherapy resistance in non-small-cell lung carcinoma" [Cancer Lett. 604 (2024) 217272].

IF 9.1 1区医学

Cancer letters Pub Date : 2024-12-27 DOI: 10.1016/j.canlet.2024.217425

Shujie Huang, Jeff Yat-Fai Chung, Chunjie Li, Yi Wu, Guibin Qiao, Ka-Fai To, Patrick Ming-Kuen Tang

引用次数: 0