首页 > 最新文献

Molecular Cancer最新文献

英文 中文
Proapoptotic activity of JNK-sensitive BH3-only proteins underpins ovarian cancer response to replication checkpoint inhibitors 仅对 JNK 敏感的 BH3 蛋白的促凋亡活性是卵巢癌对复制检查点抑制剂反应的基础
IF 37.3 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-07 DOI: 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.
最近的研究表明,复制检查点调节剂(RCMs),如 CHK1、ATR 和 WEE1 抑制剂,在实体瘤(包括铂耐药的高级别浆液性卵巢癌(HGSOC))中具有良好的单药治疗活性。然而,临床反应率通常低于 30%。虽然临床前和临床研究已对 RCM 诱导的 DNA 损伤进行了广泛研究,但复制检查点干扰与肿瘤缩小之间的联系仍未完全弄清。在这里,我们利用 HGSOC 细胞系和患者衍生异种移植(PDXs)来研究从 RCM 治疗到卵巢癌细胞死亡的过程。这些研究表明,RCM 在体外增加 CDC25A 水平和 CDK2 信号传导,导致 HGSOC 细胞系细胞周期进展失调和复制应激增加,与同源重组状态无关。这些事件导致 JNK 和多种纯 BH3 蛋白(包括 BCL2L11/BIM、BBC3/PUMA 和 BMF)相继被激活,而所有这些都是完全启动 RCM 诱导的细胞凋亡所必需的。HGSOC PDXs 对多(ADP 核糖)聚合酶抑制剂有抗药性,但对 RCMs 的体内外反应是细胞数量在三维培养中减少,体内反应是异种移植缩小或生长速度明显降低。这些发现确定了将复制检查点抑制与卵巢癌抗肿瘤反应联系起来的关键细胞死亡启动事件。
{"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}
引用次数: 0
Artificial intelligence alphafold model for molecular biology and drug discovery: a machine-learning-driven informatics investigation 用于分子生物学和药物发现的人工智能 alphafold 模型:机器学习驱动的信息学研究
IF 37.3 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 DOI: 10.1186/s12943-024-02140-6
Song-Bin Guo, Yuan Meng, Liteng Lin, Zhen-Zhong Zhou, Hai-Long Li, Xiao-Peng Tian, Wei-Juan Huang
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.
AlphaFold 模型重塑了生物学研究。然而,整个 AlphaFold 领域的大量非结构化数据需要进一步分析,以充分了解当前的研究状况并指导未来的探索。因此,本次科学计量学分析旨在利用机器学习驱动的信息学方法,识别关键研究集群,跟踪新兴趋势,并突出该领域中未充分探索的领域。定量统计分析显示,AlphaFold 领域正呈现出惊人的发展趋势(年增长率 = 180.13%)和全球合作(国际合著 = 33.33%)。无监督聚类算法、时间序列跟踪和全球影响力评估指出,聚类 3(人工智能驱动的 AlphaFold 结构生物学进展)的影响力最大(平均引用次数 = 48.36 ± 184.98)。此外,回归曲线和热点迸发分析突出表明,"结构预测"(s = 12.40,R2 = 0.9480,p = 0.0051)、"人工智能"(s = 5.00,R2 = 0.8096,p = 0.0375)、"药物发现"(s = 1.90,R2 = 0.7987,p = 0.0409)和 "分子动力学"(s = 2.40,R2 = 0.8000,p = 0.0405)是推动研究前沿的核心热点。更重要的是,Walktrap 算法进一步揭示了 "结构预测、人工智能、分子动力学"(相关百分比[RP] = 100%,发展百分比[DP] = 25.0%)、"sars-cov-2、covid-19、疫苗设计"(RP = 97.8%,DP = 37.5%)和 "同源建模、虚拟筛选、膜蛋白"(RP = 89.9%,DP = 26.1%)与 AlphaFold 模型密切相关,但仍未得到充分开发,这意味着还有广阔的探索空间。总之,通过机器学习驱动的信息学方法,本次科学计量学分析客观、全面地概述了全球AlphaFold研究,确定了关键的研究集群和热点,同时前瞻性地指出了尚未充分开发的关键领域。
{"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}
引用次数: 0
Pharmacological targeting of P300/CBP reveals EWS::FLI1-mediated senescence evasion in Ewing sarcoma. P300/CBP 的药理靶向揭示了 EWS::FLI1 在尤文肉瘤中介导的衰老逃避。
IF 27.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-05 DOI: 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}
引用次数: 0
Deciphering resistance mechanisms in cancer: final report of MATCH-R study with a focus on molecular drivers and PDX development. 解密癌症的抗药性机制:MATCH-R 研究的最终报告,重点关注分子驱动因素和 PDX 开发。
IF 27.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-04 DOI: 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.

背景:了解肿瘤的抗药性机制对于推进癌症治疗至关重要。由古斯塔夫-鲁西(Gustave Roussy)领导的前瞻性MATCH-R试验(NCT02517892)旨在通过对新鲜肿瘤活检组织的分子分析来确定癌症治疗的耐药机制。本报告介绍了2015年至2022年进行的MATCH-R研究的基因组数据分析,重点关注靶向疗法:研究对象包括接受影像引导下肿瘤活检的耐药转移性患者(pts)。在对冷冻组织活检中的肿瘤内容(TC)进行评估后,在抗癌治疗前和/或治疗后进行了靶向 NGS(10 30%)。通过将肿瘤片段植入 NOD scid gamma 小鼠体内建立了患者衍生异种移植(PDX),并扩增至五次传代:共收集了 857 名患者的 1120 份活检样本,最常见的肿瘤类型为肺癌(38.8%)、消化道癌(16.3%)和前列腺癌(14.1%)。30.9%的患者(n = 265/857)发现了分子靶向驱动基因,其中最常见的改变基因是表皮生长因子受体(EGFR)(41.5%)、表皮生长因子受体2/3(FGFR2/3)(15.5%)、ALK(11.7%)、BRAF(6.8%)和KRAS(5.7%)。此外,66.0%(n = 175/265)的患者在接受靶向治疗时进行了活检。在耐药病例中,41.1%(n = 72/175)未发现分子机制,32.0%(n = 56/175)表现出靶向耐药,25.1%(n = 44/175)表现出旁路耐药机制。对44名旁路耐药患者进行的分子图谱分析发现了51个变异基因,其中KRAS(13.7%)、PIK3CA(11.8%)、PTEN(11.8%)、NF2(7.8%)、AKT1(5.9%)和NF1(5.9%)是改变最多的基因。为45%的患者量身定制了治疗方案,并确定了耐药机制,从而将临床获益的中位时间延长了11个月。共将 341 例活检组织植入小鼠体内,成功建立了 136 个 PDX 模型,成功率为 39.9%。PDX模型可用于表皮生长因子受体(EGFR)(n = 31)、表皮生长因子受体2/3(n = 26)、KRAS(n = 18)、ALK(n = 16)、BRAF(n = 6)和NTRK(n = 2)驱动的癌症。这些模型在分子改变和药理状态方面密切再现了原始肿瘤的生物学特性,是验证克服治疗策略的宝贵模型:MATCH-R研究强调了在图像引导下进行肿瘤活检和建立PDX以确定耐药机制和指导个性化疗法的可行性,从而改善预处理转移性患者的预后。
{"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}
引用次数: 0
Correction: Nac1 promotes stemness and regulates myeloid‑derived cell status in triple‑negative breast cancer. 更正:Nac1促进三阴性乳腺癌的干性并调节髓源性细胞状态。
IF 27.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-03 DOI: 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}
引用次数: 0
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 社论表达的关切:miR-630靶向IGF1R,调节HER靶向药物的反应和HER2过度表达乳腺癌中癌细胞的整体进展
IF 37.3 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 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":"&lt;p&gt;&lt;b&gt;Correction:&lt;/b&gt;&lt;b&gt;&lt;i&gt;Mol Cancer&lt;/i&gt;&lt;/b&gt;&lt;b&gt; 13&lt;/b&gt;, &lt;b&gt;71 (2014)&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;https://doi.org/10.1186/1476-4598-13-71&lt;/b&gt;&lt;/p&gt;&lt;p&gt;&lt;b&gt;Published: 24 March 2014&lt;/b&gt;&lt;/p&gt;&lt;p&gt;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.&lt;/p&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;School of Pharmacy and Pharmaceutical Sciences &amp; Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland&lt;/p&gt;&lt;p&gt;Claire Corcoran, Sweta Rani, Susan Breslin, Martina Gogarty &amp; Lorraine O’Driscoll&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA&lt;/p&gt;&lt;p&gt;Irene M Ghobrial&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Oncology, St. Vincent’s University Hospital, Dublin 4, Ireland&lt;/p&gt;&lt;p&gt;John Crown&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Claire Corcoran&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Sweta Rani&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Susan Breslin&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Martina Gogarty&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Irene M Ghobrial&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;John Crown&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Lorraine O’Driscoll&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;h3&gt;Corresponding author&lt;/h3&gt;&lt;p&gt;Correspondence to Lorraine O’Driscoll.&lt;/p&gt;&lt;h3&gt;Publisher’s note&lt;/h3&gt;&lt;p&gt;Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.&lt;/p&gt;&lt;p&gt;The online version of the original article can be found at https://doi.org/10.1186/1476-4598-13-71.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Open Access&lt;/b&gt; 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}
引用次数: 0
Traditional Chinese medicine for the treatment of cancers of hepatobiliary system: from clinical evidence to drug discovery 中医药治疗肝胆系统癌症:从临床证据到药物发现
IF 37.3 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 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.
肝癌、胆道癌和胰腺癌因其高度恶性而成为消化系统疾病领域的重大挑战。传统中医药(TCM)作为一种潜在的治疗方法,在中国有着悠久的历史,其临床疗效也得到了广泛认可。在这篇综述中,我们系统地总结了在治疗肝癌、胆道癌和胰腺癌的临床试验中显示出良好效果的中医药临床应用。我们重点介绍了几种通过严格临床试验验证疗效的常用中药疗法,包括怀儿颗粒、华蟾素和淫羊藿苷。我们对这些活性化合物及其潜在靶点进行了深入阐释,为中医药在抗癌药物研发方面的潜力提供了宝贵的见解。我们强调了进一步研究的重要性,以弥合中医药与现代肿瘤学之间的差距,促进以证据为基础的中医药治疗这些具有挑战性的恶性肿瘤的发展。
{"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}
引用次数: 0
Chinese herbal medicine for the treatment of intestinal cancer: preclinical studies and potential clinical applications 治疗肠癌的中草药:临床前研究和潜在的临床应用
IF 37.3 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-10-01 DOI: 10.1186/s12943-024-02135-3
Juan Zhang, Yulin Wu, Yuanyang Tian, Hongxi Xu, Zhi-Xiu Lin, Yan-Fang Xian
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}
引用次数: 0
Deciphering the role of LGALS2: insights into tertiary lymphoid structure-associated dendritic cell activation and immunotherapeutic potential in breast cancer patients 解密 LGALS2 的作用:洞察乳腺癌患者的三级淋巴结构相关树突状细胞激活和免疫治疗潜力
IF 37.3 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-30 DOI: 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.
癌症研究的最新进展突显了三级淋巴结构(TLS)在调节免疫反应中的关键作用,尤其是在乳腺癌(BRCA)中。在这里,我们利用基于生物网络的计算策略和机器学习(ML)方法对来自 6000 多个 BRCA 样本的大量转录组数据进行了综合分析,并确定 LGALS2 是 TLSs 中的一个关键标记。单细胞测序和空间转录组学揭示了LGALS2在TLS相关树突状细胞(DCs)刺激中的作用,并揭示了肿瘤微环境(TME)在宏观和微观层面的复杂性。LGALS2 表达的升高与生存期的延长有关,而生存期的延长与以多样化免疫细胞浸润和活跃的抗肿瘤通路为特征的强健免疫反应有关,这导致了 "热 "肿瘤微环境。苏木精-伊红(HE)、免疫组织化学(IHC)和体内验证分析证实了LGALS2与TLS相关DC的共定位及其在BRCA免疫激活中的作用。将 LGALS2 鉴定为 BRCA 的一个关键因素,不仅凸显了它在新型 TLS 引导的免疫疗法中的治疗潜力,还为患者分层和治疗选择开辟了新途径,最终改善了临床管理。
{"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}
引用次数: 0
CircRNA and lncRNA-encoded peptide in diseases, an update review 疾病中的 CircRNA 和 lncRNA 编码肽:最新综述
IF 37.3 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-09-30 DOI: 10.1186/s12943-024-02131-7
Qian Yi, Jianguo Feng, Weiwu Lan, Houyin shi, Wei Sun, Weichao Sun
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.
非编码 RNA(ncRNA),包括环状 RNA(circRNA)和长非编码 RNA(lncRNA),是真核生物基因组中广泛存在的独特 RNA 分子。它们的失调已被发现,并在包括各种癌症在内的多种疾病的发病机制中发挥了关键作用。以前人们认为这些 ncRNA 不具备编码蛋白质的能力,但最近的研究发现,这些 ncRNA 中的少量开放阅读框(ORF)赋予了它们编码蛋白质的潜力。这些 ncRNA 衍生的多肽或蛋白质已被证实可通过不同机制调节各种生理和病理过程。它们在疾病诊断和靶向治疗中新出现的作用凸显了它们在临床中的潜在用途。本综述旨在系统地概述由 lncRNAs 和 circRNAs 编码的蛋白质或多肽,阐明它们的产生和功能机制,并探讨它们在癌症诊断、疾病预测和靶向治疗中的应用前景。
{"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}
引用次数: 0
期刊
Molecular Cancer
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1