Cancer research最新文献_第4页

Extracellular Vesicle-Packaged ACSL4 Induces Hepatocyte Senescence to Promote Hepatocellular Carcinoma Progression. 细胞外囊泡包裹的ACSL4诱导肝细胞衰老，促进肝细胞癌进展

IF 12.5 1区医学

Cancer research Pub Date : 2024-09-03 DOI: 10.1158/0008-5472.CAN-24-0832

Pei-Pei Hou, Chong-Ming Zheng, Si-Hong Wu, Xi-Xiao Liu, Guang-Xin Xiang, Wei-Yang Cai, Gang Chen, Yong-Liang Lou

{"title":"Extracellular Vesicle-Packaged ACSL4 Induces Hepatocyte Senescence to Promote Hepatocellular Carcinoma Progression.","authors":"Pei-Pei Hou, Chong-Ming Zheng, Si-Hong Wu, Xi-Xiao Liu, Guang-Xin Xiang, Wei-Yang Cai, Gang Chen, Yong-Liang Lou","doi":"10.1158/0008-5472.CAN-24-0832","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-24-0832","url":null,"abstract":"Extracellular vesicles (EVs) derived from cancer cells are crucial mediators of intercellular communication during tumor progression. The cargo in tumor-derived EVs that facilitates the establishment of a tumor-supportive microenvironment could serve as a therapeutic target to improve cancer treatment. Here, we demonstrated that hepatocellular carcinoma (HCC) cells secreted the acyl-CoA synthetase ACSL4 in large extracellular vesicles (lEVs) to modulate tumor-microenvironment interactions that promote HCC progression. HCC-derived lEV ACSL4 increased the intracellular abundance of polyunsaturated fatty acid-containing lipids and remodeled the lipid profile to potentiate lipid peroxidation in peritumoral hepatocytes, resulting in hepatocyte senescence accompanied by the senescence-associated secretory phenotype (SASP). Depletion of senescent hepatocytes by senolytic treatment suppressed tumor progression. In HCC cells, SREBP2-mediated transcriptional activation upregulated ACSL4 expression, and Akt-mediated phosphorylation of ACSL4 induced its packaging into lEVs by augmenting its interaction with Annexin A2. This study identified the critical regulatory function of ACSL4 secreted from HCC cells in inducing lipid remodeling and senescence in hepatocytes to support HCC progression, suggesting that targeting lEV ACSL4 is a potential therapeutic strategy for HCC.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124904","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

Neural Circuitries between the Brain and Peripheral Solid Tumors. 大脑与外周实体瘤之间的神经环路

IF 12.5 1区医学

Cancer research Pub Date : 2024-09-03 DOI: 10.1158/0008-5472.CAN-24-1779

Xiang Chen, Yuli Geng, Guanxin Wei, Danzeng He, Jialong Lv, Wenhao Wen, Fan Xiang, Kaixiong Tao, Chuanqing Wu

{"title":"Neural Circuitries between the Brain and Peripheral Solid Tumors.","authors":"Xiang Chen, Yuli Geng, Guanxin Wei, Danzeng He, Jialong Lv, Wenhao Wen, Fan Xiang, Kaixiong Tao, Chuanqing Wu","doi":"10.1158/0008-5472.CAN-24-1779","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-24-1779","url":null,"abstract":"The recent discovery of the pivotal role of central nervous system (CNS) in controlling tumor initiation and progression has opened a new field of research. Increasing evidence suggests a bidirectional interaction between the brain and tumors. The brain influences the biological behavior of tumor cells through complex neural networks involving the peripheral nervous system, the endocrine system, and the immune system, while tumors can establish local autonomic and sensory neural networks to transmit signals into the CNS, thereby affecting brain activity. This review aims to summarize the latest research in brain-tumor crosstalk, exploring neural circuitries between the brain and various peripheral solid tumors, analyzing the roles in tumor development and the related molecular mediators and pathological mechanisms, and highlighting the critical impact on the understanding of cancer biology. Enhanced understanding of reciprocal communication between the brain and tumors will establish a solid theoretical basis for further research and could open avenues for repurposing psychiatric interventions in cancer treatment.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124905","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

Live-Cell Invasive Phenotyping Uncovers ALK2 as a Therapeutic Target in LKB1-Mutant Lung Cancer 活细胞侵袭表型分析发现 ALK2 是 LKB1 突变肺癌的治疗靶点

IF 11.2 1区医学

Cancer research Pub Date : 2024-08-29 DOI: 10.1158/0008-5472.can-23-2631

Junghui Koo, Chang-Soo Seong, Rebecca E. Parker, Amy Herrera, Bhakti Dwivedi, Robert A. Arthur, Ashok Reddy. Dinasarapu, H. Richard. Johnston, Henry Claussen, Carol Tucker-Burden, Suresh S. Ramalingam, Haian Fu, Wei Zhou, Adam I. Marcus, Melissa Gilbert-Ross

{"title":"Live-Cell Invasive Phenotyping Uncovers ALK2 as a Therapeutic Target in LKB1-Mutant Lung Cancer","authors":"Junghui Koo, Chang-Soo Seong, Rebecca E. Parker, Amy Herrera, Bhakti Dwivedi, Robert A. Arthur, Ashok Reddy. Dinasarapu, H. Richard. Johnston, Henry Claussen, Carol Tucker-Burden, Suresh S. Ramalingam, Haian Fu, Wei Zhou, Adam I. Marcus, Melissa Gilbert-Ross","doi":"10.1158/0008-5472.can-23-2631","DOIUrl":"https://doi.org/10.1158/0008-5472.can-23-2631","url":null,"abstract":"The acquisition of invasive properties is a prerequisite for tumor progression and metastasis. Molecular subtypes of KRAS-driven lung cancer exhibit distinct modes of invasion that contribute to unique growth properties and therapeutic susceptibilities. Despite this, pre-clinical strategies designed to exploit growth within the context of invasion are lacking. To address this, we designed an experimental system to screen for targetable signaling pathways linked to active early 3D invasion phenotypes in different molecular subtypes of KRAS-driven lung adenocarcinoma (LUAD). Combined live-cell imaging of human bronchial epithelial cells in a 3D invasion matrix and transcriptomic profiling identified mutant LKB1-specific upregulation of BMP6. LKB1 loss increased BMP6 signaling, which induced the canonical iron regulatory hormone hepcidin. Intact LKB1 was necessary to maintain BMP6 signaling homeostasis and restrict ALK2/BMP6-fueled growth. Pre-clinical studies in a Kras/Lkb1-mutant syngeneic mouse model and in a xenograft model showed potent growth suppression by inhibiting the ALK2/BMP6 signaling axis with single agent inhibitors that are currently in clinical trials. Lastly, BMP6 expression was elevated in LKB1-mutant early-stage lung cancer patient tumors. These results are consistent with a model where LKB1 acts as a ‘brake’ to iron regulated growth and suggest that ALK2 inhibition can be used for patients with LKB1-mutant tumors.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100702","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

Galectin-9 Mediates the Functions of Microglia in the Hypoxic Brain Tumor Microenvironment Galectin-9 在缺氧脑肿瘤微环境中调控小胶质细胞的功能

IF 11.2 1区医学

Cancer research Pub Date : 2024-08-29 DOI: 10.1158/0008-5472.can-23-3878

Chanju Lee, Dahee Yu, Hyung-Seok Kim, Ki Sun Kim, Chi Young Chang, Hee Jung Yoon, Su Bin Won, Dae Yeon Kim, Eun Ah Goh, Yong Sun Lee, Jong Bae Park, Sang Soo Kim, Eun Jung Park

{"title":"Galectin-9 Mediates the Functions of Microglia in the Hypoxic Brain Tumor Microenvironment","authors":"Chanju Lee, Dahee Yu, Hyung-Seok Kim, Ki Sun Kim, Chi Young Chang, Hee Jung Yoon, Su Bin Won, Dae Yeon Kim, Eun Ah Goh, Yong Sun Lee, Jong Bae Park, Sang Soo Kim, Eun Jung Park","doi":"10.1158/0008-5472.can-23-3878","DOIUrl":"https://doi.org/10.1158/0008-5472.can-23-3878","url":null,"abstract":"Galectin-9 is a multifaceted regulator of various pathophysiological processes that exerts positive or negative effects in a context-dependent manner. Here, we elucidated the distinctive functional properties of galectin-9 on myeloid cells within the brain tumor microenvironment. Galectin-9-expressing cells were abundant at the hypoxic tumor edge in the tumor-bearing ipsilateral hemisphere compared to the contralateral hemisphere in an intracranial mouse brain tumor model. Galectin-9 was highly expressed in microglia and macrophages in tumor-infiltrating cells. In primary glia, both the expression and secretion of galectin-9 were influenced by tumors. Analysis of a human glioblastoma bulk RNA-sequencing dataset and a single-cell RNA-sequencing dataset from a murine glioma model revealed a correlation between galectin-9 expression and glial cell activation. Notably, the galectin-9high microglial subset was functionally distinct from the galectin-9neg/low subset in the brain tumor microenvironment. Galectin-9high microglia exhibited properties of inflammatory activation and higher rates of cell death, whereas galectin-9neg/low microglia displayed a superior phagocytic ability against brain tumor cells. Blockade of galectin-9 suppressed tumor growth and altered the activity of glial and T cells in a mouse glioma model. Additionally, glial galectin-9 expression was regulated by Hif-2α in the hypoxic brain tumor microenvironment. Myeloid-specific Hif-2α deficiency led to attenuated tumor progression. Together, these findings reveal that galectin-9 on myeloid cells is an immunoregulator and putative therapeutic target in brain tumors.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":11.2,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100703","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

Tumour's Digest: Macrophage metabolism creates a barrier to T cells. 肿瘤文摘巨噬细胞的新陈代谢为 T 细胞提供了屏障

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-26 DOI: 10.1158/0008-5472.CAN-24-3039

Eleanor Jane Tyler, Oliver M T Pearce

引用次数: 0

Fitness Screens Map State-Specific Glioblastoma Stem Cell Vulnerabilities. 体能筛选绘制出特定状态的胶质母细胞瘤干细胞脆弱性图。

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-26 DOI: 10.1158/0008-5472.CAN-23-4024

Graham MacLeod, Fatemeh Molaei, Shahan Haider, Maira P Almeida, Sichun Lin, Michelle Kushida, Haresh Sureshkumar, Jasmine K Bhatti, Jack Q Lu, Daniel Schramek, Peter B Dirks, Stephane Angers

{"title":"Fitness Screens Map State-Specific Glioblastoma Stem Cell Vulnerabilities.","authors":"Graham MacLeod, Fatemeh Molaei, Shahan Haider, Maira P Almeida, Sichun Lin, Michelle Kushida, Haresh Sureshkumar, Jasmine K Bhatti, Jack Q Lu, Daniel Schramek, Peter B Dirks, Stephane Angers","doi":"10.1158/0008-5472.CAN-23-4024","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-4024","url":null,"abstract":"Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults and is driven by self-renewing glioblastoma stem cells (GSCs) that persist after therapy and seed treatment refractory recurrent tumors. GBM tumors display a high degree of intra- and inter-tumoral heterogeneity that is a prominent barrier to targeted treatment strategies. This heterogeneity extends to GSCs that exist on a gradient between two transcriptional states or subtypes termed developmental and injury-response. Drug targets for each subtype are needed to effectively target GBM. To identify conserved and subtype-specific genetic dependencies across a large and heterogeneous panel of GSCs, we designed the GBM5K targeted gRNA library and performed fitness screens in a total of 30 patient-derived GSC cultures. The focused CRISPR screens identified the most conserved subtype-specific vulnerabilities in GSCs and elucidated the functional dependency gradient existing between the developmental and injury-response states. Developmental-specific fitness genes were enriched for transcriptional regulators of neurodevelopment, whereas injury-response-specific fitness genes were highlighted by several genes implicated in integrin and focal adhesion signaling. These context-specific vulnerabilities conferred differential sensitivity to inhibitors of β1 integrin, FAK, MEK and OLIG2. Interestingly, the screens revealed that the subtype-specific signaling pathways drive differential cyclin D (CCND1 vs. CCND2) dependencies between subtypes. These data provide biological insight and mechanistic understanding of GBM heterogeneity and point to opportunities for precision targeting of defined GBM and GSC subtypes to tackle heterogeneity.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072097","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

Bottom-up or Top-down: Inflammation Reprograms Paneth Cells to Develop Bowel Cancers. 自下而上还是自上而下？炎症重编程使肠细胞发展成肠癌

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-26 DOI: 10.1158/0008-5472.CAN-24-3073

Julian Chua, Alex Gregorieff, Arshad Ayyaz

{"title":"Bottom-up or Top-down: Inflammation Reprograms Paneth Cells to Develop Bowel Cancers.","authors":"Julian Chua, Alex Gregorieff, Arshad Ayyaz","doi":"10.1158/0008-5472.CAN-24-3073","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-24-3073","url":null,"abstract":"The origins of colorectal cancer (CRC) have long been a subject of intense debate. Early observations noted cancer formation in the human gut slightly above the base of crypts, the structural and functional units of the regenerative compartment of the intestinal epithelium. This suggested that the cells of origin for CRC reside close to the crypt-villus junction, where more differentiated cells are located. However, the specific induction of early cancer-initiating mutations within differentiated cells failed to initiate cancer. The subsequent identification of long-lived Lgr5+ intestinal stem cells and investigations into their role in cancer development further shifted the earlier views, leading to the widely accepted theory that CRC arises from stem cells and progenitors located at the base of crypts. A recent study published in Nature Genetics by Mathijs P. Verhagen and colleagues challenges this paradigm, providing compelling evidence that differentiated non-stem cell lineages, particularly Paneth cells, can serve as a source of intestinal tumorigenesis, especially in the context of inflammation and the consumption of a Western-style diet. This work significantly advances our understanding of the CRC initiation process and provides a new paradigm that may explain the increasingly higher incidence of CRC in younger people.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072068","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

Targeting Galectin-1 Overcomes Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma. 靶向 Galectin-1 克服食管鳞状细胞癌的紫杉醇耐药性

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-26 DOI: 10.1158/0008-5472.CAN-23-2241

Liting Zhou, Jie Tian, Keke Wang, Yijie Ma, Xiaojie Chen, Hui Luo, Bingbing Lu, Nan Wang, Penglei Wang, Xuejiao Liu, Ran Zhao, Simin Zhao, Jiutao Wang, Wenna Nie, Hong Ge, Wenting Liu, Tingxuan Gu, Kangdong Liu, Mee-Hyun Lee, Xiang Li, Zigang Dong

{"title":"Targeting Galectin-1 Overcomes Paclitaxel Resistance in Esophageal Squamous Cell Carcinoma.","authors":"Liting Zhou, Jie Tian, Keke Wang, Yijie Ma, Xiaojie Chen, Hui Luo, Bingbing Lu, Nan Wang, Penglei Wang, Xuejiao Liu, Ran Zhao, Simin Zhao, Jiutao Wang, Wenna Nie, Hong Ge, Wenting Liu, Tingxuan Gu, Kangdong Liu, Mee-Hyun Lee, Xiang Li, Zigang Dong","doi":"10.1158/0008-5472.CAN-23-2241","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-2241","url":null,"abstract":"Resistance to paclitaxel poses a major obstacle in esophageal squamous cell carcinoma (ESCC) treatment. A better understanding of the mechanisms underlying paclitaxel resistance could help identify prognostic biomarkers and improved therapeutic strategies. In this study, we established a patient-derived xenograft (PDX) model of acquired paclitaxel resistance and used RNA-sequencing to identify galectin-1, encoded by LGALS1, as a key mediator of resistance. Integrative analysis of clinical data and physiological studies indicated that serum galectin-1 levels were elevated in resistant patients and correlated with treatment outcomes before and during taxane therapy. Importantly, exposing cells to serum from resistant patients resulted in increased paclitaxel resistance compared to serum from sensitive patients, which was closely associated with galectin-1 concentrations in the serum. The specific clearance of galectin-1 from resistant patient serum significantly restored paclitaxel sensitivity, and inhibiting galectin-1, through knockdown or the pharmacologic inhibitor OTX008, increased sensitivity to paclitaxel. Galectin-1 inhibition reduced the activity of β-catenin, thereby inhibiting stem cell properties induced by the Wnt/β-catenin pathway. Furthermore, galectin-1 regulated MDR1 transcription through increased nuclear accumulation of β-catenin, thus increasing resistance to paclitaxel. Combining OTX008 with clinical taxane formulations effectively reversed paclitaxel resistance in vitro and in vivo. Elevated galectin-1 levels thus serve as an indicator of response to paclitaxel therapy in ESCC, offering a therapeutic intervention strategy to overcome drug resistance.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072101","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

CRISPR Screening of Transcribed Super-Enhancers Identifies Drivers of Triple-Negative Breast Cancer Progression. CRISPR 筛选转录超级增强子，发现三阴性乳腺癌进展的驱动因素。

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-26 DOI: 10.1158/0008-5472.CAN-23-3995

Michael W Lewis, Caitlin M King, Kamila Wisniewska, Matthew J Regner, Alisha Coffey, Michael R Kelly, Raul Mendez-Giraldez, Eric S Davis, Douglas H Phanstiel, Hector L Franco

{"title":"CRISPR Screening of Transcribed Super-Enhancers Identifies Drivers of Triple-Negative Breast Cancer Progression.","authors":"Michael W Lewis, Caitlin M King, Kamila Wisniewska, Matthew J Regner, Alisha Coffey, Michael R Kelly, Raul Mendez-Giraldez, Eric S Davis, Douglas H Phanstiel, Hector L Franco","doi":"10.1158/0008-5472.CAN-23-3995","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-3995","url":null,"abstract":"Triple-negative breast cancer (TNBC) is the most therapeutically recalcitrant form of breast cancer, which is due in part to the paucity of targeted therapies. A systematic analysis of regulatory elements that extend beyond protein coding genes could uncover avenues for therapeutic intervention. To this end, we analyzed the regulatory mechanisms of TNBC-specific transcriptional enhancers together with their non-coding enhancer RNA (eRNA) transcripts. The functions of the top 30 eRNA-producing super-enhancers were systematically probed using high-throughput CRISPR-interference assays coupled to RNA-seq that enabled unbiased detection of target genes genome-wide. Generation of high resolution Hi-C chromatin interaction maps enabled annotation of the direct target genes for each super-enhancer, which highlighted their proclivity for genes that portend worse clinical outcomes in TNBC patients. Illustrating the utility of this dataset, deletion of an identified super-enhancer controlling the nearby PODXL gene or specific degradation of its enhancer RNAs led to profound inhibitory effects on target gene expression, cell proliferation, and migration. Furthermore, loss of this super-enhancer suppressed tumor growth and metastasis in TNBC mouse xenograft models. Single-cell RNA-seq and ATAC-seq analyses demonstrated the enhanced activity of this super-enhancer within the malignant cells of TNBC tumor specimens compared to non-malignant cell types. Collectively, this work examines several fundamental questions about how regulatory information encoded into eRNA-producing super-enhancers drives gene expression networks that underlie the biology of triple-negative breast cancer.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072069","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

Molecular Characterization and Classification of HER2-Positive Breast Cancer Inform Tailored Therapeutic Strategies. HER2 阳性乳腺癌的分子特征和分类为定制治疗策略提供依据。

IF 12.5 1区医学

Cancer research Pub Date : 2024-08-26 DOI: 10.1158/0008-5472.CAN-23-4066

Yu-Wei Li, Lei-Jie Dai, Xiang-Rong Wu, Shen Zhao, Yu-Zheng Xu, Xi Jin, Yi Xiao, Ying Wang, Cai-Jin Lin, Yi-Fan Zhou, Tong Fu, Wen-Tao Yang, Ming Li, Hong Lv, Siyuan Chen, Anita Grigoriadis, Yi-Zhou Jiang, Ding Ma, Zhi-Ming Shao

{"title":"Molecular Characterization and Classification of HER2-Positive Breast Cancer Inform Tailored Therapeutic Strategies.","authors":"Yu-Wei Li, Lei-Jie Dai, Xiang-Rong Wu, Shen Zhao, Yu-Zheng Xu, Xi Jin, Yi Xiao, Ying Wang, Cai-Jin Lin, Yi-Fan Zhou, Tong Fu, Wen-Tao Yang, Ming Li, Hong Lv, Siyuan Chen, Anita Grigoriadis, Yi-Zhou Jiang, Ding Ma, Zhi-Ming Shao","doi":"10.1158/0008-5472.CAN-23-4066","DOIUrl":"https://doi.org/10.1158/0008-5472.CAN-23-4066","url":null,"abstract":"HER2-positive breast cancer is an aggressive subtype that accounts for 15-20% of all breast cancers. Recent studies have suggested that HER2-positive breast cancer is a group of heterogeneous diseases with different sensitivities to standard treatment regimens. Revealing the molecular heterogeneity of HER2-positive breast cancer could potentially enable more precise treatment strategies. Here, we performed multiomics profiling on a HER2-positive breast cancer cohort and identified four transcriptome-based subtypes. The classical HER2 (HER2-CLA) subtype comprised 28.3% of the samples and displayed high ERBB2 activation and significant benefit from anti-HER2 therapy. The immunomodulatory (HER2-IM) subtype (20%) featured an immune-activated microenvironment, potentially suitable for de-escalated treatment and immunotherapy. The luminal-like (HER2-LUM) subtype (30.6%) possessed similar molecular features of hormone receptor-positive HER2-negative breast cancer, suggesting endocrine therapy and CDK4/6 inhibitors as a potential therapeutic strategy. Lastly, the basal/mesenchymal-like (HER2-BM) subtype (21.1%), had a poor response to current anti-HER2 dual-targeted therapies and could potentially benefit from tyrosine kinase inhibitors. The molecular characteristics and clinical features of the subtypes were further explored across multiple cohorts, and the feasibility of the proposed treatment strategies was validated in patient-derived organoid and patient-derived tumor fragment models. This study elucidates the molecular heterogeneity of HER2-positive breast cancer and paves the way for a more tailored treatment.","PeriodicalId":9441,"journal":{"name":"Cancer research","volume":null,"pages":null},"PeriodicalIF":12.5,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072099","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