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":"12 1","pages":""},"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":"1 1","pages":""},"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":"23 1","pages":"222"},"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":"23 1","pages":"221"},"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":"23 1","pages":"220"},"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
{"title":"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","authors":"Claire Corcoran, Sweta Rani, Susan Breslin, Martina Gogarty, Irene M Ghobrial, John Crown, Lorraine O’Driscoll","doi":"10.1186/s12943-024-02139-z","DOIUrl":"https://doi.org/10.1186/s12943-024-02139-z","url":null,"abstract":"<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","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"7 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360352","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 : 2024-10-01DOI: 10.1186/s12943-024-02136-2
Junyu Wu, Guoyi Tang, Chien-Shan Cheng, Ranna Yeerken, Yau-Tuen Chan, Zhiwen Fu, Yi-Chao Zheng, Yibin Feng, Ning Wang
Hepatic, biliary, and pancreatic cancer pose significant challenges in the field of digestive system diseases due to their highly malignant nature. Traditional Chinese medicine (TCM) has gained attention as a potential therapeutic approach with long-standing use in China and well-recognized clinical benefits. In this review, we systematically summarized the clinical applications of TCM that have shown promising results in clinical trials in treating hepatic, biliary, and pancreatic cancer. We highlighted several commonly used TCM therapeutics with validated efficacy through rigorous clinical trials, including Huaier Granule, Huachansu, and Icaritin. The active compounds and their potential targets have been thoroughly elucidated to offer valuable insights into the potential of TCM for anti-cancer drug discovery. We emphasized the importance of further research to bridge the gap between TCM and modern oncology, facilitating the development of evidence-based TCM treatment for these challenging malignancies.
{"title":"Traditional Chinese medicine for the treatment of cancers of hepatobiliary system: from clinical evidence to drug discovery","authors":"Junyu Wu, Guoyi Tang, Chien-Shan Cheng, Ranna Yeerken, Yau-Tuen Chan, Zhiwen Fu, Yi-Chao Zheng, Yibin Feng, Ning Wang","doi":"10.1186/s12943-024-02136-2","DOIUrl":"https://doi.org/10.1186/s12943-024-02136-2","url":null,"abstract":"Hepatic, biliary, and pancreatic cancer pose significant challenges in the field of digestive system diseases due to their highly malignant nature. Traditional Chinese medicine (TCM) has gained attention as a potential therapeutic approach with long-standing use in China and well-recognized clinical benefits. In this review, we systematically summarized the clinical applications of TCM that have shown promising results in clinical trials in treating hepatic, biliary, and pancreatic cancer. We highlighted several commonly used TCM therapeutics with validated efficacy through rigorous clinical trials, including Huaier Granule, Huachansu, and Icaritin. The active compounds and their potential targets have been thoroughly elucidated to offer valuable insights into the potential of TCM for anti-cancer drug discovery. We emphasized the importance of further research to bridge the gap between TCM and modern oncology, facilitating the development of evidence-based TCM treatment for these challenging malignancies. ","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"58 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360304","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}
Intestinal cancer (IC) poses a significant global health challenge that drives continuous efforts to explore effective treatment modalities. Conventional treatments for IC are effective, but are associated with several limitations and drawbacks. Chinese herbal medicine (CHM) plays an important role in the overall cancer prevention and therapeutic strategies. Recent years have seen a growing body of research focus on the potential of CHM in IC treatment, showing promising results in managing IC and mitigating the adverse effects of radiotherapy and chemotherapy. This review provides updated information from preclinical research and clinical observation on CHM’s role in treatment of IC, offering insights into its comprehensive management and guiding future prevention strategies and clinical practice.
肠癌(IC)对全球健康构成重大挑战,促使人们不断努力探索有效的治疗方法。肠癌的传统治疗方法虽然有效,但也存在一些局限性和弊端。中草药在整个癌症预防和治疗策略中发挥着重要作用。近年来,越来越多的研究聚焦于中药在 IC 治疗中的潜力,在控制 IC 和减轻放疗和化疗的不良反应方面取得了可喜的成果。本综述提供了有关 CHM 在 IC 治疗中作用的临床前研究和临床观察的最新信息,为 IC 的综合管理提供了见解,并为未来的预防策略和临床实践提供指导。
{"title":"Chinese herbal medicine for the treatment of intestinal cancer: preclinical studies and potential clinical applications","authors":"Juan Zhang, Yulin Wu, Yuanyang Tian, Hongxi Xu, Zhi-Xiu Lin, Yan-Fang Xian","doi":"10.1186/s12943-024-02135-3","DOIUrl":"https://doi.org/10.1186/s12943-024-02135-3","url":null,"abstract":"Intestinal cancer (IC) poses a significant global health challenge that drives continuous efforts to explore effective treatment modalities. Conventional treatments for IC are effective, but are associated with several limitations and drawbacks. Chinese herbal medicine (CHM) plays an important role in the overall cancer prevention and therapeutic strategies. Recent years have seen a growing body of research focus on the potential of CHM in IC treatment, showing promising results in managing IC and mitigating the adverse effects of radiotherapy and chemotherapy. This review provides updated information from preclinical research and clinical observation on CHM’s role in treatment of IC, offering insights into its comprehensive management and guiding future prevention strategies and clinical practice.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"27 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360534","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 : 2024-09-30DOI: 10.1186/s12943-024-02126-4
Shuyu Li, Nan Zhang, Hao Zhang, Zhifang Yang, Quan Cheng, Kang Wei, Meng Zhou, Chenshen Huang
Recent advances in cancer research have highlighted the pivotal role of tertiary lymphoid structures (TLSs) in modulating immune responses, particularly in breast cancer (BRCA). Here, we performed an integrated analysis of bulk transcriptome data from over 6000 BRCA samples using biological network-based computational strategies and machine learning (ML) methods, and identified LGALS2 as a key marker within TLSs. Single-cell sequencing and spatial transcriptomics uncover the role of LGALS2 in TLS-associated dendritic cells (DCs) stimulation and reveal the complexity of the tumor microenvironment (TME) at both the macro and micro levels. Elevated LGALS2 expression correlates with prolonged survival, which is associated with a robust immune response marked by diverse immune cell infiltration and active anti-tumor pathways leading to a ‘hot’ tumor microenvironment. The colocalization of LGALS2 with TLS-associated DCs and its role in immune activation in BRCA were confirmed by hematoxylin-eosin (HE), immunohistochemistry (IHC), and in vivo validation analyses. The identification of LGALS2 as a key factor in BRCA not only highlights its therapeutic potential in novel TLS-directed immunotherapy but also opens new avenues in patient stratification and treatment selection, ultimately improving clinical management.
{"title":"Deciphering the role of LGALS2: insights into tertiary lymphoid structure-associated dendritic cell activation and immunotherapeutic potential in breast cancer patients","authors":"Shuyu Li, Nan Zhang, Hao Zhang, Zhifang Yang, Quan Cheng, Kang Wei, Meng Zhou, Chenshen Huang","doi":"10.1186/s12943-024-02126-4","DOIUrl":"https://doi.org/10.1186/s12943-024-02126-4","url":null,"abstract":"Recent advances in cancer research have highlighted the pivotal role of tertiary lymphoid structures (TLSs) in modulating immune responses, particularly in breast cancer (BRCA). Here, we performed an integrated analysis of bulk transcriptome data from over 6000 BRCA samples using biological network-based computational strategies and machine learning (ML) methods, and identified LGALS2 as a key marker within TLSs. Single-cell sequencing and spatial transcriptomics uncover the role of LGALS2 in TLS-associated dendritic cells (DCs) stimulation and reveal the complexity of the tumor microenvironment (TME) at both the macro and micro levels. Elevated LGALS2 expression correlates with prolonged survival, which is associated with a robust immune response marked by diverse immune cell infiltration and active anti-tumor pathways leading to a ‘hot’ tumor microenvironment. The colocalization of LGALS2 with TLS-associated DCs and its role in immune activation in BRCA were confirmed by hematoxylin-eosin (HE), immunohistochemistry (IHC), and in vivo validation analyses. The identification of LGALS2 as a key factor in BRCA not only highlights its therapeutic potential in novel TLS-directed immunotherapy but also opens new avenues in patient stratification and treatment selection, ultimately improving clinical management.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"37 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330314","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}
Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy.
{"title":"CircRNA and lncRNA-encoded peptide in diseases, an update review","authors":"Qian Yi, Jianguo Feng, Weiwu Lan, Houyin shi, Wei Sun, Weichao Sun","doi":"10.1186/s12943-024-02131-7","DOIUrl":"https://doi.org/10.1186/s12943-024-02131-7","url":null,"abstract":"Non-coding RNAs (ncRNAs), including circular RNAs (circRNAs) and long non-coding RNAs (lncRNAs), are unique RNA molecules widely identified in the eukaryotic genome. Their dysregulation has been discovered and played key roles in the pathogenesis of numerous diseases, including various cancers. Previously considered devoid of protein-coding ability, recent research has revealed that a small number of open reading frames (ORFs) within these ncRNAs endow them with the potential for protein coding. These ncRNAs-derived peptides or proteins have been proven to regulate various physiological and pathological processes through diverse mechanisms. Their emerging roles in disease diagnosis and targeted therapy underscore their potential utility in clinical settings. This comprehensive review aims to provide a systematic overview of proteins or peptides encoded by lncRNAs and circRNAs, elucidate their production and functional mechanisms, and explore their promising applications in cancer diagnosis, disease prediction, and targeted therapy.","PeriodicalId":19000,"journal":{"name":"Molecular Cancer","volume":"32 1","pages":""},"PeriodicalIF":37.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142330315","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}