{"title":"Abstract 1208: Identifying a novel glycolytic inhibitor for treatment of aggressive prostate cancer","authors":"Tanya Stoyanova","doi":"10.1158/1538-7445.AM2021-1208","DOIUrl":null,"url":null,"abstract":"Among men, prostate cancer is the second leading cause of cancer-associated mortality, with advanced disease remaining a major clinical challenge. Chalcones are a major class of widely occurring natural products that are intermediates in plant flavonoid isoflavonoid synthesis. They are characterized by an α,β-unsaturated carbonyl structure with two aromatic rings and commonly act as free-radical scavengers. Herein, we describe a chalcone derivative, SU086, as an anticancer agent for prostate cancer. Proteomic and metabolomic profiling demonstrate that SU086 impairs glycolysis, a critical pathway for cancer growth and survival. SU086 inhibited prostate cancer cell growth, migration, and invasion in vitro. Moreover, SU086 significantly delayed the tumor growth of cell line-derived xenograft models of CRPC as well as patient-derived xenografts (PDXs) in vivo, and the proliferation of primary human prostate cancer patient-derived tissues ex vivo. Furthermore, SU086 strongly synergized with standard of care second-generation anti-androgens, enzalutamide and abiraterone, in inhibiting prostate cancer cell growth in vitro and tumor growth in vivo. Our study identifies SU086 alone or in combination therapy settings as a novel treatment for aggressive prostate cancer. We demonstrate that SU086 represents a highly effective therapeutic strategy for both AR-sensitive and AR-insensitive prostate cancers and may potentially be applicable across multiple cancer types. Citation Format: Tanya Ivanova Stoyanova. Identifying a novel glycolytic inhibitor for treatment of aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1208.","PeriodicalId":12258,"journal":{"name":"Experimental and Molecular Therapeutics","volume":"12 1","pages":""},"PeriodicalIF":0.0000,"publicationDate":"2021-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Experimental and Molecular Therapeutics","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1158/1538-7445.AM2021-1208","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Among men, prostate cancer is the second leading cause of cancer-associated mortality, with advanced disease remaining a major clinical challenge. Chalcones are a major class of widely occurring natural products that are intermediates in plant flavonoid isoflavonoid synthesis. They are characterized by an α,β-unsaturated carbonyl structure with two aromatic rings and commonly act as free-radical scavengers. Herein, we describe a chalcone derivative, SU086, as an anticancer agent for prostate cancer. Proteomic and metabolomic profiling demonstrate that SU086 impairs glycolysis, a critical pathway for cancer growth and survival. SU086 inhibited prostate cancer cell growth, migration, and invasion in vitro. Moreover, SU086 significantly delayed the tumor growth of cell line-derived xenograft models of CRPC as well as patient-derived xenografts (PDXs) in vivo, and the proliferation of primary human prostate cancer patient-derived tissues ex vivo. Furthermore, SU086 strongly synergized with standard of care second-generation anti-androgens, enzalutamide and abiraterone, in inhibiting prostate cancer cell growth in vitro and tumor growth in vivo. Our study identifies SU086 alone or in combination therapy settings as a novel treatment for aggressive prostate cancer. We demonstrate that SU086 represents a highly effective therapeutic strategy for both AR-sensitive and AR-insensitive prostate cancers and may potentially be applicable across multiple cancer types. Citation Format: Tanya Ivanova Stoyanova. Identifying a novel glycolytic inhibitor for treatment of aggressive prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1208.