Poster Presentations - Proffered Abstracts最新文献

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Abstract P183: CRISPR screens identify sensitizers to trametinib in KRAS mutant cancer cell lines P183: CRISPR筛选在KRAS突变癌细胞系中鉴定出对曲美替尼的致敏物
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p183
Silvia Fenoglio, Aileen M. Cristo, James Tepper, T. Teng, Samuel R. Meier, Ashley H Choi, Hongxiang Zhang, Shan-Chuan Zhao, Shangtao Liu, Leanne G. Ahronian, Daniel Aird, Nikitha Das, Yi Yu, R. T. Sjin, Jannik N Andersen, A. Huang, Fang Li, Xuewen Pan
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引用次数: 0
Abstract P197: An anti-HER3 antibody, HMBD-001, that uniquely binds to and blocks the HER3 heterodimerization interface, shows superior tumor growth inhibition in biomarker-defined preclinical cancer models including NRG1-fusion driven cancers 摘要:抗HER3抗体HMBD-001独特地结合并阻断HER3异源二聚化界面,在生物标志物定义的临床前癌症模型(包括nrg1融合驱动的癌症)中显示出卓越的肿瘤生长抑制作用
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p197
D. Thakkar, Shalini Paliwal, S. Kar, N. Gandhi, Konrad H. Paszkiewicz, P. Ingram, J. Boyd-Kirkup
{"title":"Abstract P197: An anti-HER3 antibody, HMBD-001, that uniquely binds to and blocks the HER3 heterodimerization interface, shows superior tumor growth inhibition in biomarker-defined preclinical cancer models including NRG1-fusion driven cancers","authors":"D. Thakkar, Shalini Paliwal, S. Kar, N. Gandhi, Konrad H. Paszkiewicz, P. Ingram, J. Boyd-Kirkup","doi":"10.1158/1535-7163.targ-21-p197","DOIUrl":"https://doi.org/10.1158/1535-7163.targ-21-p197","url":null,"abstract":"","PeriodicalId":20348,"journal":{"name":"Poster Presentations - Proffered Abstracts","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83095605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
Abstract P028: Proteomic approaches define rocaglates as translation remodelers with multiple protein targets 摘要:蛋白质组学方法将螺旋蛋白定义为具有多个蛋白靶点的翻译重塑蛋白
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p028
Tyler A. Cunningham, J. Ho, P. Manara, Stephen Lee, J. Schatz
{"title":"Abstract P028: Proteomic approaches define rocaglates as translation remodelers with multiple protein targets","authors":"Tyler A. Cunningham, J. Ho, P. Manara, Stephen Lee, J. Schatz","doi":"10.1158/1535-7163.targ-21-p028","DOIUrl":"https://doi.org/10.1158/1535-7163.targ-21-p028","url":null,"abstract":"Intro: Deregulated protein synthesis is a common trait across solid and hematologic malignancies and an attractive target for cancer therapy. Rocaglates compounds that inhibit eukaryotic initiation factor 4A1 (eIF4A1), the essential DEAD-box RNA helicase that resolves mRNA 5'UTR secondary structures during cap-dependent translation initiation. Rocaglates' unique mechanism of action causes sequence-selective mRNA binding by eIF4A1, clamping the inactive helicase onto the transcript. This suppresses translation globally and affects many oncogenic and pro-survival transcripts in particular. Zotatifin, the first-in class synthetic rocaglate, is currently in Phase I clinical trials for the treatment of solid tumors and as an antiviral against SARS-CoV2. Currently, eIF4A1 and DDX3 are the only reported targets of rocaglate-mediated RNA clamping. Employing unbiased proteomic approaches, we have discovered that rocaglates, thought to act as pure eIF4A/translation inhibitors, extensively remodel the translation machinery and translatome. Additionally, mass-spec interrogation for proteins interacting with specific RNA sequences reveals novel targets of rocaglate-mediated, sequence-specific RNA clamping. Methods: We conducted original mass-spectrometry analyses of translational reprogramming by rocaglates. TMT-pSILAC assessed acute changes in protein production, while MATRIX, which captures high-resolution profiles of the translation machinery, revealed translation factors that drive reprogramming in response to rocaglate exposure. We validated results biochemically, in cellulo, and in vivo using patient-derived xenograft (PDX) mouse models. To probe existing and novel rocaglate RNA-clamping targets, we developed unbiased “clampome” assays - in cellulo protein-RNA-pull downs followed by mass-spec analysis of proteins with increased binding to RNA in the presence of rocaglates. Results: We find rocaglates, including zotatifin, have effects far more complex than simple “translational inhibition” as currently defined. Indeed, translatome analysis by TMT-pSILAC revealed myriad up-regulated proteins that drive hitherto unrecognized cytotoxic mechanisms. The GEF-H1 guanine exchange factor, for example, drives anti-survival RHOA/JNK activation, suggesting novel candidate biomarkers of rocaglate clinical outcomes. Translation-machinery analysis by MATRIX identifed rocaglate-induced dependence on specific translation factors including eEF1ϵ1 that drive remodeling. Novel rocaglate RNA-binding targets revealed by clampome studies remain under detailed evaluation as mediators of drug activities. Discussion: Our original proteome-level interrogation revealed that the complete cellular response to these historical “translation inhibitors” is mediated by comprehensive translational landscape remodeling. Effects on a broader suite of RNA binding proteins than eIF4A1 alone we suggest mediate the potent antitumor activities of these unique compounds, elucidation of which per","PeriodicalId":20348,"journal":{"name":"Poster Presentations - Proffered Abstracts","volume":"2013 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87896294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract P145: The RNA helicase EIF4A is a therapeutic vulnerability in triple-negative breast cancer P145: RNA解旋酶EIF4A是三阴性乳腺癌的治疗易感性
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p145
N. Zhao, J. Rosen
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引用次数: 0
Abstract P066: Gain and loss of function genome-wide CRISPR screens identify Hippo signalling as an important driver of resistance in EGFR mutant lung cancer P066:功能获得和功能丧失的全基因组CRISPR筛选发现Hippo信号是EGFR突变肺癌耐药的重要驱动因素
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p066
M. Pfeifer, Jonathan S. Brammeld, S. Price, Matthew J. Martin, H. Thorpe, A. Bornot, Ercia Banks, N. Guan, S. Dunn, Maria Lisa Guerriero, Daniel O'Neill, J. Pilling, Davide Gianni, J. Brownell, Paul D. Smith, Ultan McDermott
{"title":"Abstract P066: Gain and loss of function genome-wide CRISPR screens identify Hippo signalling as an important driver of resistance in EGFR mutant lung cancer","authors":"M. Pfeifer, Jonathan S. Brammeld, S. Price, Matthew J. Martin, H. Thorpe, A. Bornot, Ercia Banks, N. Guan, S. Dunn, Maria Lisa Guerriero, Daniel O'Neill, J. Pilling, Davide Gianni, J. Brownell, Paul D. Smith, Ultan McDermott","doi":"10.1158/1535-7163.targ-21-p066","DOIUrl":"https://doi.org/10.1158/1535-7163.targ-21-p066","url":null,"abstract":"","PeriodicalId":20348,"journal":{"name":"Poster Presentations - Proffered Abstracts","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88881948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract P260: Development and validation of a novel T-cell modulating, microbiome-based peptide for combination with immunotherapy P260:开发和验证一种新的t细胞调节,微生物为基础的肽结合免疫治疗
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p260
Michelle Lin, A. Nagaraja, D. Haria, Y. Katlinskaya, D. Ravichandar, Preston Williams, Roberta L Hannibal, T. DeSantis, B. Hwang, Michael Wilcoxon, T. Takeuchi, K. Dabbagh, P. Lal, H. Kiefel
{"title":"Abstract P260: Development and validation of a novel T-cell modulating, microbiome-based peptide for combination with immunotherapy","authors":"Michelle Lin, A. Nagaraja, D. Haria, Y. Katlinskaya, D. Ravichandar, Preston Williams, Roberta L Hannibal, T. DeSantis, B. Hwang, Michael Wilcoxon, T. Takeuchi, K. Dabbagh, P. Lal, H. Kiefel","doi":"10.1158/1535-7163.targ-21-p260","DOIUrl":"https://doi.org/10.1158/1535-7163.targ-21-p260","url":null,"abstract":"","PeriodicalId":20348,"journal":{"name":"Poster Presentations - Proffered Abstracts","volume":"251 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73372114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract P077: SCO-101 mediates re-sensitization of irinotecan (SN38) resistant colorectal cancer cells 摘要P077: SCO-101介导伊立替康(SN38)耐药结直肠癌细胞的再致敏
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p077
J. Stenvang, N. L. Roest, P. M. Vestlev, B. Hansen
{"title":"Abstract P077: SCO-101 mediates re-sensitization of irinotecan (SN38) resistant colorectal cancer cells","authors":"J. Stenvang, N. L. Roest, P. M. Vestlev, B. Hansen","doi":"10.1158/1535-7163.targ-21-p077","DOIUrl":"https://doi.org/10.1158/1535-7163.targ-21-p077","url":null,"abstract":"","PeriodicalId":20348,"journal":{"name":"Poster Presentations - Proffered Abstracts","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75983223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract P046: ENGOT-ov60/GOG3052/RAMP 201: A phase 2 study of VS-6766 (dual RAF/MEK inhibitor) alone and in combination with defactinib (FAK inhibitor) in recurrent low-grade serous ovarian cancer (LGSOC) ENGOT-ov60/GOG3052/RAMP 201: VS-6766(双RAF/MEK抑制剂)单独和联合defactinib (FAK抑制剂)治疗复发性低级别浆液性卵巢癌(LGSOC)的2期研究
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p046
Susana Banerjee, B. Monk, E. Van Nieuwenhuysen, K. Moore, A. Oaknin, M. Fabbro, Nicoletta Columbo, D. O’Malley, R. Coleman, J. Pachter, A. Koustenis, Gloria Patrick, Lorna Leonard, R. Grisham
{"title":"Abstract P046: ENGOT-ov60/GOG3052/RAMP 201: A phase 2 study of VS-6766 (dual RAF/MEK inhibitor) alone and in combination with defactinib (FAK inhibitor) in recurrent low-grade serous ovarian cancer (LGSOC)","authors":"Susana Banerjee, B. Monk, E. Van Nieuwenhuysen, K. Moore, A. Oaknin, M. Fabbro, Nicoletta Columbo, D. O’Malley, R. Coleman, J. Pachter, A. Koustenis, Gloria Patrick, Lorna Leonard, R. Grisham","doi":"10.1158/1535-7163.targ-21-p046","DOIUrl":"https://doi.org/10.1158/1535-7163.targ-21-p046","url":null,"abstract":"","PeriodicalId":20348,"journal":{"name":"Poster Presentations - Proffered Abstracts","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76166423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
Abstract P049: Phase II trial of TRC102 (methoxyamine HCl) in combination with temozolomide (TMZ) in patients with advanced non-small cell lung cancer P049: TRC102(甲氧基胺HCl)联合替莫唑胺(TMZ)治疗晚期非小细胞肺癌的II期临床试验
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p049
M. Salkeni, G. Coyne, Jennifer Zlott, N. Takebe, N. Ma, L. Rubinstein, R. Piekarz, Jared C. Foster, Brandon Miller, R. Parchment, A. Naqash, A. Voth, J. Doroshow, A. Chen
{"title":"Abstract P049: Phase II trial of TRC102 (methoxyamine HCl) in combination with temozolomide (TMZ) in patients with advanced non-small cell lung cancer","authors":"M. Salkeni, G. Coyne, Jennifer Zlott, N. Takebe, N. Ma, L. Rubinstein, R. Piekarz, Jared C. Foster, Brandon Miller, R. Parchment, A. Naqash, A. Voth, J. Doroshow, A. Chen","doi":"10.1158/1535-7163.targ-21-p049","DOIUrl":"https://doi.org/10.1158/1535-7163.targ-21-p049","url":null,"abstract":"","PeriodicalId":20348,"journal":{"name":"Poster Presentations - Proffered Abstracts","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77441548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Abstract P136: Response to alpelisib in an adolescent with PIK3CA-mutated metastatic gastrointestinal stromal tumour P136: alpelisib治疗pik3ca突变的青少年转移性胃肠道间质瘤的疗效
Poster Presentations - Proffered Abstracts Pub Date : 2021-12-01 DOI: 10.1158/1535-7163.targ-21-p136
S. Cohen-Gogo, Nisha Kanwar, Furqan Shaikh, R. Baertschiger, A. Shlien, D. Malkin, J. Putra, Ailish C. Coblentz, A. Villani, Abha A. Gupta, D. Morgenstern
{"title":"Abstract P136: Response to alpelisib in an adolescent with PIK3CA-mutated metastatic gastrointestinal stromal tumour","authors":"S. Cohen-Gogo, Nisha Kanwar, Furqan Shaikh, R. Baertschiger, A. Shlien, D. Malkin, J. Putra, Ailish C. Coblentz, A. Villani, Abha A. Gupta, D. Morgenstern","doi":"10.1158/1535-7163.targ-21-p136","DOIUrl":"https://doi.org/10.1158/1535-7163.targ-21-p136","url":null,"abstract":"","PeriodicalId":20348,"journal":{"name":"Poster Presentations - Proffered Abstracts","volume":"102 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74026246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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