Cancer Chemistry最新文献

{"title":"Abstract 288: Revisiting small molecules that influence the nuclear translocation of thioredoxin-1, prohibitin, and galectin-3 for cancer chemotherapy","authors":"J. Fortin, Thomas E. Wineland, Kelsey E. Duggan, R. C.-Gaudreault","doi":"10.1158/1538-7445.AM2021-288","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2021-288","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"39 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85757581","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}

{"title":"Abstract 3419: Lymph node colonization promotes distant tumor metastasis through the induction of tumor-specific immunosuppression","authors":"Nathan E. Reticker-Flynn, P. Basto, Weiruo Zhang, M. M. Martins, Serena Chang, A. Gentles, J. Sunwoo, S. Plevritis, E. Engleman","doi":"10.1158/1538-7445.am2020-3419","DOIUrl":"https://doi.org/10.1158/1538-7445.am2020-3419","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"121 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81381027","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}

{"title":"Abstract 5690: Discovery of JNJ-67856633: A novel, first-in-class MALT1 protease inhibitor for the treatment of B cell lymphomas","authors":"U. Philippar, T. Lu, N. Vloemans, M. Bekkers, L. van Nuffel, M. Gaudiano, K. Wnuk-Lipinska, B. van der Leede, K. Amssoms, K. Kimpe, B. Medaer, T. Greway, Yann Abraham, M. Cummings, E. Trella, G. Vanhoof, Weimei Sun, J. Thuring, P. Connolly, J. Linders, H. Rui, S. Balasubramanian, A. Johnson, J. Gerecitano, J. Goldberg, J. Edwards, Y. Elsayed, J. Smit, J. Bussolari, R. Attar","doi":"10.1158/1538-7445.am2020-5690","DOIUrl":"https://doi.org/10.1158/1538-7445.am2020-5690","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"89 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84241331","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}

{"title":"Abstract 1067: Proteogenomic discovery of novel tumor proteins as neoantigens for personalized T cell immunotherapy in pediatric medulloblastoma","authors":"S. Rivero-Hinojosa, M. Grant, A. Panigrahi, Huizhen Zhang, V. Caisová, C. Bollard, Brian R. Rood","doi":"10.1158/1538-7445.am2020-1067","DOIUrl":"https://doi.org/10.1158/1538-7445.am2020-1067","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"140 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86730144","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}

{"title":"Abstract 5691: SM08502, a novel, small-molecule CDC-like kinase (CLK) inhibitor, demonstrates strong antitumor effects and Wnt pathway inhibition in castration-resistant prostate cancer (CRPC) models","authors":"C. Bossard, Nathalia Cruz, K. Chiu, Brian W. Eastman, C. Mak, S. Kc, Gail Bucci, J. Stewart, T. Phalen, S. Cha","doi":"10.1158/1538-7445.am2020-5691","DOIUrl":"https://doi.org/10.1158/1538-7445.am2020-5691","url":null,"abstract":"CRPC is associated with primary and acquired chemotherapy resistance. Loss of androgen receptor (AR) signaling or development of AR splicing variants (e.g., ARV7) in CRPC imparts resistance to standard of care (SOC) agents that target AR signaling (e.g., enzalutamide and abiraterone). Effective therapies are an unmet need for CRPC patients with treatment-resistant tumors. Aberrant Wnt pathway activation contributes to resistance to AR-targeted agents, and cytotoxic chemotherapies such as docetaxel have been shown to activate Wnt signaling in PC cells. SM08502 has demonstrated strong antitumor activity in several preclinical cancer models and has been shown to inhibit the Wnt signaling pathway via disruption of alternative splicing. Here, we examined the antitumor activity of SM08502 in preclinical models of CRPC. The effect of SM08502 on cell proliferation was tested in 5 PC cell lines. Proliferation was strongly impaired by SM08502 across all cell lines (average EC50=0.319 μM [0.191–0.462]) irrespective of their mutation profile or hormone sensitivity. Compared to DMSO, SM08502 inhibited serine/arginine-rich splicing factor 6 (SRSF6) phosphorylation and potently suppressed Wnt-related gene (LRP5, TCF7, TCF7L1) and protein expression. In vivo antitumor effects and tolerability of QD oral SM08502 were assessed in multiple xenograft models, including mice bearing 22RV1 (ARV7+) or PC3 (AR-/-) CRPC flank xenografts (n=6/group). In 22RV1 xenografts, tumor growth inhibition (TGI) was demonstrated in mice treated with 12 and 25 mg/kg SM08502 (35%, P In summary, SM08502 potently inhibited cell proliferation, SRSF6 phosphorylation, and Wnt-related gene expression in multiple PC cell lines. In vivo, SM08502 demonstrated strong antitumor effects in CRPC xenografts. These data suggest that SM08502 has the potential to provide clinical benefit to patients with treatment-resistant CRPC. A Phase 1 study of SM08502 in subjects with advanced solid tumors is ongoing (NCT03355066). Citation Format: Carine Bossard, Nathalia Cruz, Kevin Chiu, Brian Eastman, Chi Ching Mak, Sunil KC, Gail Bucci, Josh Stewart, Timothy J. Phalen, Steven Cha. SM08502, a novel, small-molecule CDC-like kinase (CLK) inhibitor, demonstrates strong antitumor effects and Wnt pathway inhibition in castration-resistant prostate cancer (CRPC) models [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5691.","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79520831","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}

{"title":"Abstract 3418: A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) SWOG S1609: The salivary gland tumor cohort","authors":"Y. Chae, M. Othus, S. Patel, J. Ohr, F. Worden, J. Suga, A. Naing, Sarah E Fenton, Hyunseok Kang, Sewan Gurung, Christine M. McLeod, F. Giles, Helen X. Chen, E. Sharon, E. Mayerson, M. Plets, C. Ryan, C. Blanke, R. Kurzrock","doi":"10.1158/1538-7445.am2020-3418","DOIUrl":"https://doi.org/10.1158/1538-7445.am2020-3418","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"20 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72900564","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}

{"title":"Abstract 2762: Development of a novel peptide-formed nanoparticle for pancreatic cancer treatment","authors":"Qiongling Wang, K. Staveley-O’Carroll, Guangfu Li","doi":"10.1158/1538-7445.SABCS18-2762","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-2762","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73642477","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}

{"title":"Abstract 3: Discovery and optimization of small molecule Bax activators for cancer therapy","authors":"Gang Liu, Hyejin Kim, C. Ding, Zhu-huan Yu, Hong Wang, Haiying Chen, Q. Shen, Jia Zhou","doi":"10.1158/1538-7445.SABCS18-3","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-3","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73801095","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}

{"title":"Abstract 997: Three-dimensional high-throughput drug screening for bladder cancer","authors":"Sang-Cheol Lee, Young Saing Kim, I. Hwang, Su Jin Lee, S. Park","doi":"10.1158/1538-7445.AM2019-997","DOIUrl":"https://doi.org/10.1158/1538-7445.AM2019-997","url":null,"abstract":"Recent progress in understanding the molecular mechanisms that underlie bladder cancer carcinogenesis offers the prospect of specifically targeting signaling pathways to achieve more effective and rational treatment. In a novel, 3-dimensional high-throughput drug screening (3D HTS) platform to identify novel agents affecting bladder cancer cells, 24 molecularly-targeted agents were screened in seven human bladder cancer cell lines (UCUM3, T24, SW780, RT4, J82, 5637 and 253J-BV). The efficacy of 24 targeted agents on the bladder cell lines varied dramatically on their genomic alterations. BEZ235 (mTOR and PI3K inhibitor) showed antitumor effect in most of cell lines except UMUC3. Another mTOR inhibitor, AZD2014 (inhibitors of mTORC1 and mTORC2) also had IC50 Note: This abstract was not presented at the meeting. Citation Format: Sang-Cheol Lee, Young Saing Kim, In Gyu Hwang, Su Jin Lee, Se Hoon Park. Three-dimensional high-throughput drug screening for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 997.","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74717446","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}

{"title":"Abstract 3627: Development of CLENs for future treatment & diagnostic detection using cell models of drug-resistant ovarian cancer","authors":"N. Amini, Joshua Emerson, J. Clement","doi":"10.1158/1538-7445.SABCS18-3627","DOIUrl":"https://doi.org/10.1158/1538-7445.SABCS18-3627","url":null,"abstract":"","PeriodicalId":9563,"journal":{"name":"Cancer Chemistry","volume":"38 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79390466","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}