Pub Date : 2024-10-11DOI: 10.1186/s12943-024-02138-0
Ki-Jun Ryu, Ki Won Lee, Seung-Ho Park, Taeyoung Kim, Keun-Seok Hong, Hyemin Kim, Minju Kim, Dong Woo Ok, Gu Neut Bom Kwon, Young-Jun Park, Hyuk-Kwon Kwon, Cheol Hwangbo, Kwang Dong Kim, J Eugene Lee, Jiyun Yoo
Breast cancer remains a significant health concern, with triple-negative breast cancer (TNBC) being an aggressive subtype with poor prognosis. Epithelial-mesenchymal transition (EMT) is important in early-stage tumor to invasive malignancy progression. Snail, a central EMT component, is tightly regulated and may be subjected to proteasomal degradation. We report a novel proteasomal independent pathway involving chaperone-mediated autophagy (CMA) in Snail degradation, mediated via its cytosolic interaction with HSC70 and lysosomal targeting, which prevented its accumulation in luminal-type breast cancer cells. Conversely, Snail predominantly localized to the nucleus, thus evading CMA-mediated degradation in TNBC cells. Starvation-induced CMA activation downregulated Snail in TNBC cells by promoting cytoplasmic translocation. Evasion of CMA-mediated Snail degradation induced EMT, and enhanced metastatic potential of luminal-type breast cancer cells. Our findings elucidate a previously unrecognized role of CMA in Snail regulation, highlight its significance in breast cancer, and provide a potential therapeutic target for clinical interventions.
{"title":"Chaperone-mediated autophagy modulates Snail protein stability: implications for breast cancer metastasis.","authors":"Ki-Jun Ryu, Ki Won Lee, Seung-Ho Park, Taeyoung Kim, Keun-Seok Hong, Hyemin Kim, Minju Kim, Dong Woo Ok, Gu Neut Bom Kwon, Young-Jun Park, Hyuk-Kwon Kwon, Cheol Hwangbo, Kwang Dong Kim, J Eugene Lee, Jiyun Yoo","doi":"10.1186/s12943-024-02138-0","DOIUrl":"10.1186/s12943-024-02138-0","url":null,"abstract":"<p><p>Breast cancer remains a significant health concern, with triple-negative breast cancer (TNBC) being an aggressive subtype with poor prognosis. Epithelial-mesenchymal transition (EMT) is important in early-stage tumor to invasive malignancy progression. Snail, a central EMT component, is tightly regulated and may be subjected to proteasomal degradation. We report a novel proteasomal independent pathway involving chaperone-mediated autophagy (CMA) in Snail degradation, mediated via its cytosolic interaction with HSC70 and lysosomal targeting, which prevented its accumulation in luminal-type breast cancer cells. Conversely, Snail predominantly localized to the nucleus, thus evading CMA-mediated degradation in TNBC cells. Starvation-induced CMA activation downregulated Snail in TNBC cells by promoting cytoplasmic translocation. Evasion of CMA-mediated Snail degradation induced EMT, and enhanced metastatic potential of luminal-type breast cancer cells. Our findings elucidate a previously unrecognized role of CMA in Snail regulation, highlight its significance in breast cancer, and provide a potential therapeutic target for clinical interventions.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11468019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-11DOI: 10.1186/s12943-024-02146-0
Su Yin Lim, Ines Pires da Silva, Nurudeen A. Adegoke, Serigne N. Lo, Alexander M. Menzies, Matteo S. Carlino, Richard A. Scolyer, Georgina V. Long, Jenny H. Lee, Helen Rizos
Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, providing significant benefit to patients across various tumour types, including melanoma. However, around 40% of melanoma patients do not benefit from ICI treatment, and accurately predicting ICI response remains challenging. We now describe a novel and simple approach that integrates immune-associated transcriptome signatures and tumour volume burden to better predict ICI response in melanoma patients. RNA sequencing was performed on pre-treatment (PRE) tumour specimens derived from 32 patients with advanced melanoma treated with combination PD1 and CTLA4 inhibitors. Of these 32 patients, 11 also had early during treatment (EDT, 5–15 days after treatment start) tumour samples. Tumour volume was assessed at PRE for all 32 patients, and at first computed tomography (CT) imaging for the 11 patients with EDT samples. Analysis of the Hallmark IFNγ gene set revealed no association with ICI response at PRE (AUC ROC curve = 0.6404, p = 0.24, 63% sensitivity, 71% specificity). When IFNg activity was evaluated with tumour volume (ratio of gene set expression to tumour volume) using logistic regression to predict ICI response, we observed high discriminative power in separating ICI responders from non-responders (AUC = 0.7760, p = 0.02, 88% sensitivity, 67% specificity); this approach was reproduced with other immune-associated transcriptomic gene sets. These findings were further replicated in an independent cohort of 23 melanoma patients treated with PD1 inhibitor. Hence, integrating tumour volume with immune-associated transcriptomic signatures improves the prediction of ICI response, and suggest that higher levels of immune activation relative to tumour burden are required for durable ICI response.
{"title":"Size matters: integrating tumour volume and immune activation signatures predicts immunotherapy response","authors":"Su Yin Lim, Ines Pires da Silva, Nurudeen A. Adegoke, Serigne N. Lo, Alexander M. Menzies, Matteo S. Carlino, Richard A. Scolyer, Georgina V. Long, Jenny H. Lee, Helen Rizos","doi":"10.1186/s12943-024-02146-0","DOIUrl":"https://doi.org/10.1186/s12943-024-02146-0","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) have transformed cancer treatment, providing significant benefit to patients across various tumour types, including melanoma. However, around 40% of melanoma patients do not benefit from ICI treatment, and accurately predicting ICI response remains challenging. We now describe a novel and simple approach that integrates immune-associated transcriptome signatures and tumour volume burden to better predict ICI response in melanoma patients. RNA sequencing was performed on pre-treatment (PRE) tumour specimens derived from 32 patients with advanced melanoma treated with combination PD1 and CTLA4 inhibitors. Of these 32 patients, 11 also had early during treatment (EDT, 5–15 days after treatment start) tumour samples. Tumour volume was assessed at PRE for all 32 patients, and at first computed tomography (CT) imaging for the 11 patients with EDT samples. Analysis of the Hallmark IFNγ gene set revealed no association with ICI response at PRE (AUC ROC curve = 0.6404, p = 0.24, 63% sensitivity, 71% specificity). When IFNg activity was evaluated with tumour volume (ratio of gene set expression to tumour volume) using logistic regression to predict ICI response, we observed high discriminative power in separating ICI responders from non-responders (AUC = 0.7760, p = 0.02, 88% sensitivity, 67% specificity); this approach was reproduced with other immune-associated transcriptomic gene sets. These findings were further replicated in an independent cohort of 23 melanoma patients treated with PD1 inhibitor. Hence, integrating tumour volume with immune-associated transcriptomic signatures improves the prediction of ICI response, and suggest that higher levels of immune activation relative to tumour burden are required for durable ICI response.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142405205","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}
Pub Date : 2024-10-09DOI: 10.1186/s12943-024-02141-5
Ruohan Yang, Jiuwei Cui
Compared to other types of tumor vaccines, RNA vaccines have emerged as promising alternatives to conventional vaccine therapy due to their high efficiency, rapid development capability, and potential for low-cost manufacturing and safe drug delivery. RNA vaccines mainly include mRNA, circular RNA (circRNA), and Self-amplifying mRNA(SAM). Different RNA vaccine platforms for different tumors have shown encouraging results in animal and human models. This review comprehensively describes the advances and applications of RNA vaccines in antitumor therapy. Future directions for extending this promising vaccine platform to a wide range of therapeutic uses are also discussed.
{"title":"Advances and applications of RNA vaccines in tumor treatment","authors":"Ruohan Yang, Jiuwei Cui","doi":"10.1186/s12943-024-02141-5","DOIUrl":"https://doi.org/10.1186/s12943-024-02141-5","url":null,"abstract":"Compared to other types of tumor vaccines, RNA vaccines have emerged as promising alternatives to conventional vaccine therapy due to their high efficiency, rapid development capability, and potential for low-cost manufacturing and safe drug delivery. RNA vaccines mainly include mRNA, circular RNA (circRNA), and Self-amplifying mRNA(SAM). Different RNA vaccine platforms for different tumors have shown encouraging results in animal and human models. This review comprehensively describes the advances and applications of RNA vaccines in antitumor therapy. Future directions for extending this promising vaccine platform to a wide range of therapeutic uses are also discussed.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142385474","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}
<p><b>Correction:</b> <b><i>Mol Cancer</i></b> <b>23, 213 (2024)</b></p><p><b>https://doi.org/10.1186/s12943-024-02132-6</b></p><p>Following publication of the original article [1], the authors noticed that the Funding information was not indicated in the article. The details of Funding were included in the revised manuscript that was submitted by the author to production system. The Funding information is given below. The original article has been corrected.</p><p><b>Funding</b></p><p>This work was supported by the National Science and Technology Major Project (Nos. 2023ZD0500102), the National Natural Science Foundation of China (Nos. 82270634), and Clinical Young Talent Project, Eagle breeding Team of Meng Chao Tengfei Project (Eastern Hepatobiliary Surgery Hospital).</p><ol data-track-component="outbound reference" data-track-context="references section"><li data-counter="1."><p>Shi J, Zhang Z, Yin H, et al. RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy. Mol Cancer. 2024;23:213. https://doi.org/10.1186/s12943-024-02132-6.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden="true" focusable="false" height="16" role="img" width="16"><use xlink:href="#icon-eds-i-download-medium" xmlns:xlink="http://www.w3.org/1999/xlink"></use></svg></p><span>Author notes</span><ol><li><p>Jun-xiao Shi, Zhi-chao Zhang, Hao-zan Yin, and Xian-jie Piao contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China</p><p>Jun-xiao Shi, Zhi-chao Zhang, Xian-jie Piao, Cheng-hu Liu, Qian-jia Liu, Jia-cheng Zhang, Wen-xuan Zhou, Fu-chen Liu, Yue-fan Wang & Hui Liu</p></li><li><p>The Department of Medical Genetics, Naval Medical University, Shanghai, 200433, China</p><p>Hao-zan Yin & Fu Yang</p></li><li><p>Key Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China</p><p>Fu Yang</p></li><li><p>Shanghai Key Laboratory of Medical Biodefense, Shanghai, 200433, China</p><p>Fu Yang</p></li></ol><span>Authors</span><ol><li><span>Jun-xiao Shi</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Zhi-chao Zhang</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Hao-zan Yin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xian-jie Piao</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Cheng-hu Liu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Qian-jia Liu</span>View author p
更正：Mol Cancer 23, 213 (2024)https://doi.org/10.1186/s12943-024-02132-6Following 原文[1]发表后，作者注意到文章中未标注资助信息。作者在提交给生产系统的修订稿中包含了详细的资助信息。资助信息如下。本文得到了国家科技重大专项（编号：2023ZD0500102）、国家自然科学基金（编号：82270634）、临床青年人才项目、孟超腾飞计划雏鹰培育团队（东方肝胆外科医院）的支持。Mol Cancer.2024;23:213. https://doi.org/10.1186/s12943-024-02132-6.Article PubMed PubMed Central Google Scholar Download references作者注释施俊孝、张志超、尹浩赞和彪贤杰对本工作有同等贡献。作者和工作单位海军军医大学东方肝胆外科医院肝外三科，上海，200438 史俊晓，张志超，彪宪杰，刘成虎，刘乾嘉，张家成，周文轩，刘福臣，王月凡 &；刘辉海军军医大学医学遗传学系，中国上海，200433 殷浩赞 &；Fu Yang教育部生物安全防御重点实验室，上海，200433Fu Yang上海市医学生物防御重点实验室，上海，200433、ChinaFu Yang作者：施俊孝查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者张志超查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者殷浩赞查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者卞宪杰查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者jie PiaoView 作者发表作品您也可以在 PubMed Google ScholarCheng-hu LiuView 作者发表作品您也可以在 PubMed Google ScholarQian-jia LiuView 作者发表作品您也可以在 PubMed Google ScholarJia-cheng ZhangView作者发表论文您也可以在PubMed Google Scholar中搜索该作者Wen-xuan ZhouView作者发表论文您也可以在PubMed Google Scholar中搜索该作者Fu-chen LiuView作者发表论文您也可以在PubMed Google Scholar中搜索该作者Fu YangView作者发表论文您也可以在PubMed Google Scholar中搜索该作者Yue- fan WangView作者发表论文您也可以在PubMed Google Scholar中搜索该作者Yue- fan WangView作者发表论文fan Wang查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Hui Liu查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者通信作者Fu Yang、王月凡或刘晖。出版者注释施普林格-自然对出版地图和机构隶属关系中的管辖权主张保持中立。原文的在线版本可在以下网址找到：https://doi.org/10.1186/s12943-024-02132-6.Open Access 本文采用知识共享署名-非商业性-禁止衍生 4.0 国际许可协议进行许可，该协议允许以任何媒介或格式进行任何非商业性使用、共享、分发和复制，只要您适当注明原作者和来源，提供知识共享许可协议的链接，并说明您是否修改了许可材料。根据本许可协议，您无权分享源自本文或本文部分内容的改编材料。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中，除非在材料的信用栏中另有说明。如果材料未包含在文章的知识共享许可协议中，且您打算使用的材料不符合法律规定或超出了许可使用范围，则您需要直接获得版权所有者的许可。如需查看该许可的副本，请访问 http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsCite this articleShi, Jx., Zhang, Zc., Yin, Hz. et al. Correction：RNA m6A在铁变态反应中的修饰：对推进肿瘤免疫疗法的意义。Mol Cancer 23, 225 (2024). https://doi.org/10.1186/s12943-024-02144-2Download citationPublished: 08 October 2024DOI: https://doi.org/10.1186/s12943-024-02144-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
{"title":"Correction: RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy","authors":"Jun-xiao Shi, Zhi-chao Zhang, Hao-zan Yin, Xian-jie Piao, Cheng-hu Liu, Qian-jia Liu, Jia-cheng Zhang, Wen-xuan Zhou, Fu-chen Liu, Fu Yang, Yue-fan Wang, Hui Liu","doi":"10.1186/s12943-024-02144-2","DOIUrl":"https://doi.org/10.1186/s12943-024-02144-2","url":null,"abstract":"<p><b>Correction:</b> <b><i>Mol Cancer</i></b> <b>23, 213 (2024)</b></p><p><b>https://doi.org/10.1186/s12943-024-02132-6</b></p><p>Following publication of the original article [1], the authors noticed that the Funding information was not indicated in the article. The details of Funding were included in the revised manuscript that was submitted by the author to production system. The Funding information is given below. The original article has been corrected.</p><p><b>Funding</b></p><p>This work was supported by the National Science and Technology Major Project (Nos. 2023ZD0500102), the National Natural Science Foundation of China (Nos. 82270634), and Clinical Young Talent Project, Eagle breeding Team of Meng Chao Tengfei Project (Eastern Hepatobiliary Surgery Hospital).</p><ol data-track-component=\"outbound reference\" data-track-context=\"references section\"><li data-counter=\"1.\"><p>Shi J, Zhang Z, Yin H, et al. RNA m6A modification in ferroptosis: implications for advancing tumor immunotherapy. Mol Cancer. 2024;23:213. https://doi.org/10.1186/s12943-024-02132-6.</p><p>Article PubMed PubMed Central Google Scholar </p></li></ol><p>Download references<svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"><use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"></use></svg></p><span>Author notes</span><ol><li><p>Jun-xiao Shi, Zhi-chao Zhang, Hao-zan Yin, and Xian-jie Piao contributed equally to this work.</p></li></ol><h3>Authors and Affiliations</h3><ol><li><p>The Third Department of Hepatic Surgery, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, Shanghai, 200438, China</p><p>Jun-xiao Shi, Zhi-chao Zhang, Xian-jie Piao, Cheng-hu Liu, Qian-jia Liu, Jia-cheng Zhang, Wen-xuan Zhou, Fu-chen Liu, Yue-fan Wang & Hui Liu</p></li><li><p>The Department of Medical Genetics, Naval Medical University, Shanghai, 200433, China</p><p>Hao-zan Yin & Fu Yang</p></li><li><p>Key Laboratory of Biosafety Defense, Ministry of Education, Shanghai, 200433, China</p><p>Fu Yang</p></li><li><p>Shanghai Key Laboratory of Medical Biodefense, Shanghai, 200433, China</p><p>Fu Yang</p></li></ol><span>Authors</span><ol><li><span>Jun-xiao Shi</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Zhi-chao Zhang</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Hao-zan Yin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Xian-jie Piao</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Cheng-hu Liu</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Qian-jia Liu</span>View author p","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142384151","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}
Pub Date : 2024-10-07DOI: 10.1186/s12943-024-02125-5
Annapoorna Venkatachalam, Cristina Correia, Kevin L. Peterson, Xianon Hou, Paula A. Schneider, Annabella R. Strathman, Karen S. Flatten, Chance C. Sine, Emily A. Balczewski, Cordelia D. McGehee, Melissa C. Larson, Laura N. Duffield, X. Wei Meng, Nicole D. Vincelette, Husheng Ding, Ann L. Oberg, Fergus J. Couch, Elizabeth M. Swisher, Hu Li, S. John Weroha, Scott H. Kaufmann
Recent studies indicate that replication checkpoint modulators (RCMs) such as inhibitors of CHK1, ATR, and WEE1 have promising monotherapy activity in solid tumors, including platinum-resistant high grade serous ovarian cancer (HGSOC). However, clinical response rates are generally below 30%. While RCM-induced DNA damage has been extensively examined in preclinical and clinical studies, the link between replication checkpoint interruption and tumor shrinkage remains incompletely understood. Here we utilized HGSOC cell lines and patient-derived xenografts (PDXs) to study events leading from RCM treatment to ovarian cancer cell death. These studies show that RCMs increase CDC25A levels and CDK2 signaling in vitro, leading to dysregulated cell cycle progression and increased replication stress in HGSOC cell lines independent of homologous recombination status. These events lead to sequential activation of JNK and multiple BH3-only proteins, including BCL2L11/BIM, BBC3/PUMA and the BMF, all of which are required to fully initiate RCM-induced apoptosis. Activation of the same signaling pathway occurs in HGSOC PDXs that are resistant to poly(ADP-ribose) polymerase inhibitors but respond to RCMs ex vivo with a decrease in cell number in 3-dimensional culture and in vivo with xenograft shrinkage or a significantly diminished growth rate. These findings identify key cell death-initiating events that link replication checkpoint inhibition to antitumor response in ovarian cancer.
{"title":"Proapoptotic activity of JNK-sensitive BH3-only proteins underpins ovarian cancer response to replication checkpoint inhibitors","authors":"Annapoorna Venkatachalam, Cristina Correia, Kevin L. Peterson, Xianon Hou, Paula A. Schneider, Annabella R. Strathman, Karen S. Flatten, Chance C. Sine, Emily A. Balczewski, Cordelia D. McGehee, Melissa C. Larson, Laura N. Duffield, X. Wei Meng, Nicole D. Vincelette, Husheng Ding, Ann L. Oberg, Fergus J. Couch, Elizabeth M. Swisher, Hu Li, S. John Weroha, Scott H. Kaufmann","doi":"10.1186/s12943-024-02125-5","DOIUrl":"https://doi.org/10.1186/s12943-024-02125-5","url":null,"abstract":"Recent studies indicate that replication checkpoint modulators (RCMs) such as inhibitors of CHK1, ATR, and WEE1 have promising monotherapy activity in solid tumors, including platinum-resistant high grade serous ovarian cancer (HGSOC). However, clinical response rates are generally below 30%. While RCM-induced DNA damage has been extensively examined in preclinical and clinical studies, the link between replication checkpoint interruption and tumor shrinkage remains incompletely understood. Here we utilized HGSOC cell lines and patient-derived xenografts (PDXs) to study events leading from RCM treatment to ovarian cancer cell death. These studies show that RCMs increase CDC25A levels and CDK2 signaling in vitro, leading to dysregulated cell cycle progression and increased replication stress in HGSOC cell lines independent of homologous recombination status. These events lead to sequential activation of JNK and multiple BH3-only proteins, including BCL2L11/BIM, BBC3/PUMA and the BMF, all of which are required to fully initiate RCM-induced apoptosis. Activation of the same signaling pathway occurs in HGSOC PDXs that are resistant to poly(ADP-ribose) polymerase inhibitors but respond to RCMs ex vivo with a decrease in cell number in 3-dimensional culture and in vivo with xenograft shrinkage or a significantly diminished growth rate. These findings identify key cell death-initiating events that link replication checkpoint inhibition to antitumor response in ovarian cancer.\u0000","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142383732","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}
AlphaFold model has reshaped biological research. However, vast unstructured data in the entire AlphaFold field requires further analysis to fully understand the current research landscape and guide future exploration. Thus, this scientometric analysis aimed to identify critical research clusters, track emerging trends, and highlight underexplored areas in this field by utilizing machine-learning-driven informatics methods. Quantitative statistical analysis reveals that the AlphaFold field is enjoying an astonishing development trend (Annual Growth Rate = 180.13%) and global collaboration (International Co-authorship = 33.33%). Unsupervised clustering algorithm, time series tracking, and global impact assessment point out that Cluster 3 (Artificial Intelligence-Powered Advancements in AlphaFold for Structural Biology) has the greatest influence (Average Citation = 48.36 ± 184.98). Additionally, regression curve and hotspot burst analysis highlight “structure prediction” (s = 12.40, R2 = 0.9480, p = 0.0051), “artificial intelligence” (s = 5.00, R2 = 0.8096, p = 0.0375), “drug discovery” (s = 1.90, R2 = 0.7987, p = 0.0409), and “molecular dynamics” (s = 2.40, R2 = 0.8000, p = 0.0405) as core hotspots driving the research frontier. More importantly, the Walktrap algorithm further reveals that “structure prediction, artificial intelligence, molecular dynamics” (Relevance Percentage[RP] = 100%, Development Percentage[DP] = 25.0%), “sars-cov-2, covid-19, vaccine design” (RP = 97.8%, DP = 37.5%), and “homology modeling, virtual screening, membrane protein” (RP = 89.9%, DP = 26.1%) are closely intertwined with the AlphaFold model but remain underexplored, which implies a broad exploration space. In conclusion, through the machine-learning-driven informatics methods, this scientometric analysis offers an objective and comprehensive overview of global AlphaFold research, identifying critical research clusters and hotspots while prospectively pointing out underexplored critical areas.
{"title":"Artificial intelligence alphafold model for molecular biology and drug discovery: a machine-learning-driven informatics investigation","authors":"Song-Bin Guo, Yuan Meng, Liteng Lin, Zhen-Zhong Zhou, Hai-Long Li, Xiao-Peng Tian, Wei-Juan Huang","doi":"10.1186/s12943-024-02140-6","DOIUrl":"https://doi.org/10.1186/s12943-024-02140-6","url":null,"abstract":"AlphaFold model has reshaped biological research. However, vast unstructured data in the entire AlphaFold field requires further analysis to fully understand the current research landscape and guide future exploration. Thus, this scientometric analysis aimed to identify critical research clusters, track emerging trends, and highlight underexplored areas in this field by utilizing machine-learning-driven informatics methods. Quantitative statistical analysis reveals that the AlphaFold field is enjoying an astonishing development trend (Annual Growth Rate = 180.13%) and global collaboration (International Co-authorship = 33.33%). Unsupervised clustering algorithm, time series tracking, and global impact assessment point out that Cluster 3 (Artificial Intelligence-Powered Advancements in AlphaFold for Structural Biology) has the greatest influence (Average Citation = 48.36 ± 184.98). Additionally, regression curve and hotspot burst analysis highlight “structure prediction” (s = 12.40, R2 = 0.9480, p = 0.0051), “artificial intelligence” (s = 5.00, R2 = 0.8096, p = 0.0375), “drug discovery” (s = 1.90, R2 = 0.7987, p = 0.0409), and “molecular dynamics” (s = 2.40, R2 = 0.8000, p = 0.0405) as core hotspots driving the research frontier. More importantly, the Walktrap algorithm further reveals that “structure prediction, artificial intelligence, molecular dynamics” (Relevance Percentage[RP] = 100%, Development Percentage[DP] = 25.0%), “sars-cov-2, covid-19, vaccine design” (RP = 97.8%, DP = 37.5%), and “homology modeling, virtual screening, membrane protein” (RP = 89.9%, DP = 26.1%) are closely intertwined with the AlphaFold model but remain underexplored, which implies a broad exploration space. In conclusion, through the machine-learning-driven informatics methods, this scientometric analysis offers an objective and comprehensive overview of global AlphaFold research, identifying critical research clusters and hotspots while prospectively pointing out underexplored critical areas.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":37.3,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142377365","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}
Pub Date : 2024-10-05DOI: 10.1186/s12943-024-02115-7
Erdong Wei, Ana Mitanoska, Quinn O'Brien, Kendall Porter, MacKenzie Molina, Haseeb Ahsan, Usuk Jung, Lauren Mills, Michael Kyba, Darko Bosnakovski
Ewing sarcoma (ES) poses a significant therapeutic challenge due to the difficulty in targeting its main oncodriver, EWS::FLI1. We show that pharmacological targeting of the EWS::FLI1 transcriptional complex via inhibition of P300/CBP drives a global transcriptional outcome similar to direct knockdown of EWS::FLI1, and furthermore yields prognostic risk factors for ES patient outcome. We find that EWS::FLI1 upregulates LMNB1 via repetitive GGAA motif recognition and acetylation codes in ES cells and EWS::FLI1-permissive mesenchymal stem cells, which when reversed by P300 inhibition leads to senescence of ES cells. P300-inhibited senescent ES cells can then be eliminated by senolytics targeting the PI3K signaling pathway. The vulnerability of ES cells to this combination therapy suggests an appealing synergistic strategy for future therapeutic exploration.
尤文肉瘤（ES）的主要致癌因子EWS::FLI1很难靶向治疗，这给治疗带来了巨大挑战。我们的研究表明，通过抑制 P300/CBP 对 EWS::FLI1 转录复合物进行药理学靶向，能产生与直接敲除 EWS::FLI1 相似的全局转录结果，并能进一步产生影响 ES 患者预后的风险因素。我们发现，EWS::FLI1通过ES细胞和EWS::FLI1允许的间充质干细胞中重复的GGAA图案识别和乙酰化代码上调LMNB1，当P300抑制逆转时会导致ES细胞衰老。然后，P300抑制的衰老ES细胞可通过靶向PI3K信号通路的衰老剂消除。ES 细胞易受这种联合疗法的影响，这为未来的治疗探索提供了一种有吸引力的协同策略。
{"title":"Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma.","authors":"Erdong Wei, Ana Mitanoska, Quinn O'Brien, Kendall Porter, MacKenzie Molina, Haseeb Ahsan, Usuk Jung, Lauren Mills, Michael Kyba, Darko Bosnakovski","doi":"10.1186/s12943-024-02115-7","DOIUrl":"10.1186/s12943-024-02115-7","url":null,"abstract":"<p><p>Ewing sarcoma (ES) poses a significant therapeutic challenge due to the difficulty in targeting its main oncodriver, EWS::FLI1. We show that pharmacological targeting of the EWS::FLI1 transcriptional complex via inhibition of P300/CBP drives a global transcriptional outcome similar to direct knockdown of EWS::FLI1, and furthermore yields prognostic risk factors for ES patient outcome. We find that EWS::FLI1 upregulates LMNB1 via repetitive GGAA motif recognition and acetylation codes in ES cells and EWS::FLI1-permissive mesenchymal stem cells, which when reversed by P300 inhibition leads to senescence of ES cells. P300-inhibited senescent ES cells can then be eliminated by senolytics targeting the PI3K signaling pathway. The vulnerability of ES cells to this combination therapy suggests an appealing synergistic strategy for future therapeutic exploration.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11453018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-04DOI: 10.1186/s12943-024-02134-4
Damien Vasseur, Ludovic Bigot, Kristi Beshiri, Juan Flórez-Arango, Francesco Facchinetti, Antoine Hollebecque, Lambros Tselikas, Mihaela Aldea, Felix Blanc-Durand, Anas Gazzah, David Planchard, Ludovic Lacroix, Noémie Pata-Merci, Catline Nobre, Alice Da Silva, Claudio Nicotra, Maud Ngo-Camus, Floriane Braye, Sergey I Nikolaev, Stefan Michiels, Gérôme Jules-Clement, Ken André Olaussen, Fabrice André, Jean-Yves Scoazec, Fabrice Barlesi, Santiago Ponce, Jean-Charles Soria, Benjamin Besse, Yohann Loriot, Luc Friboulet
Background: Understanding the resistance mechanisms of tumor is crucial for advancing cancer therapies. The prospective MATCH-R trial (NCT02517892), led by Gustave Roussy, aimed to characterize resistance mechanisms to cancer treatments through molecular analysis of fresh tumor biopsies. This report presents the genomic data analysis of the MATCH-R study conducted from 2015 to 2022 and focuses on targeted therapies.
Methods: The study included resistant metastatic patients (pts) who accepted an image-guided tumor biopsy. After evaluation of tumor content (TC) in frozen tissue biopsies, targeted NGS (10 < TC < 30%) or Whole Exome Sequencing and RNA sequencing (TC > 30%) were performed before and/or after the anticancer therapy. Patient-derived xenografts (PDX) were established by implanting tumor fragments into NOD scid gamma mice and amplified up to five passages.
Results: A total of 1,120 biopsies were collected from 857 pts with the most frequent tumor types being lung (38.8%), digestive (16.3%) and prostate (14.1%) cancer. Molecular targetable driver were identified in 30.9% (n = 265/857) of the patients, with EGFR (41.5%), FGFR2/3 (15.5%), ALK (11.7%), BRAF (6.8%), and KRAS (5.7%) being the most common altered genes. Furthermore, 66.0% (n = 175/265) had a biopsy at progression on targeted therapy. Among resistant cases, 41.1% (n = 72/175) had no identified molecular mechanism, 32.0% (n = 56/175) showed on-target resistance, and 25.1% (n = 44/175) exhibited a by-pass resistance mechanism. Molecular profiling of the 44 patients with by-pass resistance identified 51 variants, with KRAS (13.7%), PIK3CA (11.8%), PTEN (11.8%), NF2 (7.8%), AKT1 (5.9%), and NF1 (5.9%) being the most altered genes. Treatment was tailored for 45% of the patients with a resistance mechanism identified leading to an 11 months median extension of clinical benefit. A total of 341 biopsies were implanted in mice, successfully establishing 136 PDX models achieving a 39.9% success rate. PDX models are available for EGFR (n = 31), FGFR2/3 (n = 26), KRAS (n = 18), ALK (n = 16), BRAF (n = 6) and NTRK (n = 2) driven cancers. These models closely recapitulate the biology of the original tumors in term of molecular alterations and pharmacological status, and served as valuable models to validate overcoming treatment strategies.
Conclusion: The MATCH-R study highlights the feasibility of on purpose image guided tumor biopsies and PDX establishment to characterize resistance mechanisms and guide personalized therapies to improve outcomes in pre-treated metastatic patients.
{"title":"Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development.","authors":"Damien Vasseur, Ludovic Bigot, Kristi Beshiri, Juan Flórez-Arango, Francesco Facchinetti, Antoine Hollebecque, Lambros Tselikas, Mihaela Aldea, Felix Blanc-Durand, Anas Gazzah, David Planchard, Ludovic Lacroix, Noémie Pata-Merci, Catline Nobre, Alice Da Silva, Claudio Nicotra, Maud Ngo-Camus, Floriane Braye, Sergey I Nikolaev, Stefan Michiels, Gérôme Jules-Clement, Ken André Olaussen, Fabrice André, Jean-Yves Scoazec, Fabrice Barlesi, Santiago Ponce, Jean-Charles Soria, Benjamin Besse, Yohann Loriot, Luc Friboulet","doi":"10.1186/s12943-024-02134-4","DOIUrl":"10.1186/s12943-024-02134-4","url":null,"abstract":"<p><strong>Background: </strong>Understanding the resistance mechanisms of tumor is crucial for advancing cancer therapies. The prospective MATCH-R trial (NCT02517892), led by Gustave Roussy, aimed to characterize resistance mechanisms to cancer treatments through molecular analysis of fresh tumor biopsies. This report presents the genomic data analysis of the MATCH-R study conducted from 2015 to 2022 and focuses on targeted therapies.</p><p><strong>Methods: </strong>The study included resistant metastatic patients (pts) who accepted an image-guided tumor biopsy. After evaluation of tumor content (TC) in frozen tissue biopsies, targeted NGS (10 < TC < 30%) or Whole Exome Sequencing and RNA sequencing (TC > 30%) were performed before and/or after the anticancer therapy. Patient-derived xenografts (PDX) were established by implanting tumor fragments into NOD scid gamma mice and amplified up to five passages.</p><p><strong>Results: </strong>A total of 1,120 biopsies were collected from 857 pts with the most frequent tumor types being lung (38.8%), digestive (16.3%) and prostate (14.1%) cancer. Molecular targetable driver were identified in 30.9% (n = 265/857) of the patients, with EGFR (41.5%), FGFR2/3 (15.5%), ALK (11.7%), BRAF (6.8%), and KRAS (5.7%) being the most common altered genes. Furthermore, 66.0% (n = 175/265) had a biopsy at progression on targeted therapy. Among resistant cases, 41.1% (n = 72/175) had no identified molecular mechanism, 32.0% (n = 56/175) showed on-target resistance, and 25.1% (n = 44/175) exhibited a by-pass resistance mechanism. Molecular profiling of the 44 patients with by-pass resistance identified 51 variants, with KRAS (13.7%), PIK3CA (11.8%), PTEN (11.8%), NF2 (7.8%), AKT1 (5.9%), and NF1 (5.9%) being the most altered genes. Treatment was tailored for 45% of the patients with a resistance mechanism identified leading to an 11 months median extension of clinical benefit. A total of 341 biopsies were implanted in mice, successfully establishing 136 PDX models achieving a 39.9% success rate. PDX models are available for EGFR (n = 31), FGFR2/3 (n = 26), KRAS (n = 18), ALK (n = 16), BRAF (n = 6) and NTRK (n = 2) driven cancers. These models closely recapitulate the biology of the original tumors in term of molecular alterations and pharmacological status, and served as valuable models to validate overcoming treatment strategies.</p><p><strong>Conclusion: </strong>The MATCH-R study highlights the feasibility of on purpose image guided tumor biopsies and PDX establishment to characterize resistance mechanisms and guide personalized therapies to improve outcomes in pre-treated metastatic patients.</p>","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142372358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-03DOI: 10.1186/s12943-024-02143-3
Chrispus Ngule, Ruyi Shi, Xingcong Ren, Hongyan Jia, Felix Oyelami, Dong Li, Younhee Park, Jinhwan Kim, Hami Hemati, Yi Zhang, Xiaofang Xiong, Andrew Shinkle, Nathan L Vanderford, Sara Bachert, Binhua P Zhou, Jianlong Wang, Jianxun Song, Xia Liu, Jin-Ming Yang
{"title":"Correction: Nac1 promotes stemness and regulates myeloid‑derived cell status in triple‑negative breast cancer.","authors":"Chrispus Ngule, Ruyi Shi, Xingcong Ren, Hongyan Jia, Felix Oyelami, Dong Li, Younhee Park, Jinhwan Kim, Hami Hemati, Yi Zhang, Xiaofang Xiong, Andrew Shinkle, Nathan L Vanderford, Sara Bachert, Binhua P Zhou, Jianlong Wang, Jianxun Song, Xia Liu, Jin-Ming Yang","doi":"10.1186/s12943-024-02143-3","DOIUrl":"10.1186/s12943-024-02143-3","url":null,"abstract":"","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":null,"pages":null},"PeriodicalIF":27.7,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11448293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365874","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.1186/s12943-024-02139-z
Claire Corcoran, Sweta Rani, Susan Breslin, Martina Gogarty, Irene M Ghobrial, John Crown, Lorraine O’Driscoll
<p><b>Correction:</b><b><i>Mol Cancer</i></b><b> 13</b>, <b>71 (2014)</b></p><p><b>https://doi.org/10.1186/1476-4598-13-71</b></p><p><b>Published: 24 March 2014</b></p><p>After the publication of this article, the publisher was alerted to an apparent panel duplication and frameshift in Fig. 4B migration (ii) SKBR3-LR NC mimic and 4 C invasion (ii) SKBR3-LR NC mimic. Because the issue was detected ten years after publication, the original images for the study are no longer available. The panel has not been replaced. Readers are urged to take caution when interpreting the content and conclusions of this article.</p><h3>Authors and Affiliations</h3><ol><li><p>School of Pharmacy and Pharmaceutical Sciences & Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland</p><p>Claire Corcoran, Sweta Rani, Susan Breslin, Martina Gogarty & Lorraine O’Driscoll</p></li><li><p>Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA</p><p>Irene M Ghobrial</p></li><li><p>Department of Oncology, St. Vincent’s University Hospital, Dublin 4, Ireland</p><p>John Crown</p></li></ol><span>Authors</span><ol><li><span>Claire Corcoran</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Sweta Rani</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Susan Breslin</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Martina Gogarty</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Irene M Ghobrial</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>John Crown</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li><li><span>Lorraine O’Driscoll</span>View author publications<p>You can also search for this author in <span>PubMed<span> </span>Google Scholar</span></p></li></ol><h3>Corresponding author</h3><p>Correspondence to Lorraine O’Driscoll.</p><h3>Publisher’s note</h3><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p><p>The online version of the original article can be found at https://doi.org/10.1186/1476-4598-13-71.</p><p><b>Open Access</b> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed mater
更正：Mol Cancer 13, 71 (2014)https://doi.org/10.1186/1476-4598-13-71Published：2014年3月24日本文发表后，出版商被提醒图4B迁移(ii) SKBR3-LR NC模拟物和4 C侵袭(ii) SKBR3-LR NC模拟物中存在明显的面板重复和帧移。由于该问题是在发表十年后才发现的，因此该研究的原始图像已不可用。面板尚未更换。请读者在解释本文内容和结论时谨慎。作者和工作单位爱尔兰都柏林 2 号都柏林圣三一学院药学和制药科学学院、三一学院生物医学科学研究所爱尔兰都柏林 2 号都柏林圣三一学院药学和制药科学学院、三一学院生物医学科学研究所克莱尔-科科伦、斯韦塔-拉尼、苏珊-布雷斯林、玛蒂娜-戈加蒂、洛林-奥德里斯科尔美国马萨诸塞州波士顿哈佛医学院达纳-法伯癌症研究所肿瘤内科艾琳-M-戈布里亚尔美国马萨诸塞州波士顿哈佛医学院达纳-法伯癌症研究所肿瘤内科艾琳-M-戈布里亚尔美国马萨诸塞州波士顿哈佛医学院达纳-法伯癌症研究所肿瘤内科艾琳-M-戈布里亚尔美国马萨诸塞州波士顿圣文森特大学医院肿瘤内科Vincent's University Hospital, Dublin 4、爱尔兰John Crown作者Claire Corcoran查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Sweta Rani查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Susan Breslin查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Martina Gogarty查看作者发表的论文您也可以在PubMed Google Scholar中搜索该作者Irene M GhobrialView 作者发表作品您也可以在 PubMed Google ScholarJohn CrownView 作者发表作品您也可以在 PubMed Google ScholarLorraine O'DriscollView 作者发表作品您也可以在 PubMed Google ScholarCorresponding authorCorrespondence to Lorraine O'Driscoll.出版者注释Springer Nature对出版地图中的管辖权主张和机构隶属关系保持中立。原始文章的在线版本可在以下网址找到：https://doi.org/10.1186/1476-4598-13-71.Open Access 本文采用知识共享署名-非商业性-禁止衍生 4.0 国际许可协议进行许可，该协议允许以任何媒介或格式进行任何非商业性使用、共享、分发和复制，只要您适当注明原作者和来源，提供知识共享许可协议的链接，并说明您是否修改了许可材料。根据本许可协议，您无权分享源自本文或本文部分内容的改编材料。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中，除非在材料的信用栏中另有说明。如果材料未包含在文章的知识共享许可协议中，且您打算使用的材料不符合法律规定或超出了许可使用范围，则您需要直接获得版权所有者的许可。要查看该许可的副本，请访问 http://creativecommons.org/licenses/by-nc-nd/4.0/.Reprints and permissionsCite this articleCorcoran, C., Rani, S., Breslin, S. et al. Editorial expression of concern: miR-630 targets IGF1R to regulate response to HER-targeting drugs and overall cancer cell progression in HER2 over-expressing breast cancer.Mol Cancer 23, 219 (2024). https://doi.org/10.1186/s12943-024-02139-zDownload citationPublished: 01 October 2024DOI: https://doi.org/10.1186/s12943-024-02139-zShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative
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