Abstract 1208: Identifying a novel glycolytic inhibitor for treatment of aggressive prostate cancer

Tanya Stoyanova
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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.
摘要1208:鉴定一种治疗侵袭性前列腺癌的新型糖酵解抑制剂
在男性中,前列腺癌是癌症相关死亡的第二大原因,晚期疾病仍然是一个主要的临床挑战。查尔酮是一类广泛存在的天然产物,是植物类黄酮异黄酮合成的中间体。它们具有α,β-不饱和羰基结构和两个芳香环,通常作为自由基清除剂。在这里,我们描述了一种查尔酮衍生物SU086,作为前列腺癌的抗癌剂。蛋白质组学和代谢组学分析表明,SU086损害糖酵解,这是癌症生长和生存的关键途径。SU086在体外抑制前列腺癌细胞的生长、迁移和侵袭。此外,SU086在体内显著延缓了CRPC细胞系来源的异种移植物模型和患者来源的异种移植物(PDXs)的肿瘤生长,以及原发性人前列腺癌患者来源组织的体外增殖。此外,SU086与标准治疗的第二代抗雄激素恩杂鲁胺和阿比特龙在体外抑制前列腺癌细胞生长和体内抑制肿瘤生长方面具有很强的协同作用。我们的研究确定SU086单独或联合治疗是一种治疗侵袭性前列腺癌的新方法。我们证明SU086对于ar敏感性和ar不敏感性前列腺癌都是一种非常有效的治疗策略,并且可能适用于多种癌症类型。引用格式:Tanya Ivanova Stoyanova。鉴定一种治疗侵袭性前列腺癌的新型糖酵解抑制剂[摘要]。见:美国癌症研究协会2021年年会论文集;2021年4月10日至15日和5月17日至21日。费城(PA): AACR;癌症杂志,2021;81(13 -增刊):摘要第1208期。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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