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在向去势抵抗性前列腺癌进展的过程中,可药物治疗的代谢脆弱性被暴露和掩盖。

Druggable Metabolic Vulnerabilities Are Exposed and Masked during Progression to Castration Resistant Prostate Cancer.

机构信息

Vancouver Prostate Centre, Vancouver, BC V6H 3Z6, Canada.

Department of Urologic Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V5Z 1M9, Canada.

出版信息

Biomolecules. 2022 Oct 28;12(11):1590. doi: 10.3390/biom12111590.

DOI:10.3390/biom12111590
PMID:36358940
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9687810/
Abstract

There is an urgent need for exploring new actionable targets other than androgen receptor to improve outcome from lethal castration-resistant prostate cancer. Tumor metabolism has reemerged as a hallmark of cancer that drives and supports oncogenesis. In this regard, it is important to understand the relationship between distinctive metabolic features, androgen receptor signaling, genetic drivers in prostate cancer, and the tumor microenvironment (symbiotic and competitive metabolic interactions) to identify metabolic vulnerabilities. We explore the links between metabolism and gene regulation, and thus the unique metabolic signatures that define the malignant phenotypes at given stages of prostate tumor progression. We also provide an overview of current metabolism-based pharmacological strategies to be developed or repurposed for metabolism-based therapeutics for castration-resistant prostate cancer.

摘要

迫切需要探索除雄激素受体以外的新的可操作靶点,以改善致命性去势抵抗性前列腺癌的预后。肿瘤代谢已重新成为癌症的一个标志,它推动并支持肿瘤发生。在这方面,了解独特的代谢特征、雄激素受体信号、前列腺癌中的遗传驱动因素以及肿瘤微环境(共生和竞争代谢相互作用)之间的关系,以确定代谢弱点非常重要。我们探讨了代谢与基因调控之间的联系,从而确定了在前列腺肿瘤进展的特定阶段定义恶性表型的独特代谢特征。我们还概述了目前基于代谢的药理学策略,以开发或重新用于基于代谢的治疗去势抵抗性前列腺癌的方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/cf145d274545/biomolecules-12-01590-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/6e6037debf05/biomolecules-12-01590-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/493439c2872d/biomolecules-12-01590-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/0b09f5ba9cd9/biomolecules-12-01590-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/cf145d274545/biomolecules-12-01590-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/6e6037debf05/biomolecules-12-01590-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/493439c2872d/biomolecules-12-01590-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/0b09f5ba9cd9/biomolecules-12-01590-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7a0/9687810/cf145d274545/biomolecules-12-01590-g004.jpg

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本文引用的文献

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De Novo Design of an Androgen Receptor DNA Binding Domain-Targeted peptide PROTAC for Prostate Cancer Therapy.从头设计一种雄激素受体 DNA 结合域靶向肽 PROTAC 用于前列腺癌治疗。
Adv Sci (Weinh). 2022 Oct;9(28):e2201859. doi: 10.1002/advs.202201859. Epub 2022 Aug 15.
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Dysregulated lipolysis and lipophagy in lipid droplets of macrophages from high fat diet-fed obese mice.高脂肪饮食喂养肥胖小鼠的巨噬细胞脂滴中脂肪分解和脂噬的失调。
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3
Sirpiglenastat (DRP-104) Induces Antitumor Efficacy through Direct, Broad Antagonism of Glutamine Metabolism and Stimulation of the Innate and Adaptive Immune Systems.
癌细胞中的代谢异质性、可塑性以及对“谷氨酰胺成瘾”的适应性:谷氨酰胺酶和GTωA[谷氨酰胺转氨酶-ω-酰胺酶(谷氨酰胺酶II)]途径的作用
Biology (Basel). 2023 Aug 14;12(8):1131. doi: 10.3390/biology12081131.
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A new tumorgraft panel to accelerate precision medicine in prostate cancer.一种加速前列腺癌精准医学发展的新型肿瘤移植模型
Front Oncol. 2023 May 26;13:1130048. doi: 10.3389/fonc.2023.1130048. eCollection 2023.
Sirpiglenastat(DRP - 104)通过直接广泛拮抗谷氨酰胺代谢以及刺激先天性和适应性免疫系统来诱导抗肿瘤疗效。
Mol Cancer Ther. 2022 Oct 7;21(10):1561-1572. doi: 10.1158/1535-7163.MCT-22-0282.
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Metabolic analysis as a driver for discovery, diagnosis, and therapy.代谢分析作为发现、诊断和治疗的驱动力。
Cell. 2022 Jul 21;185(15):2678-2689. doi: 10.1016/j.cell.2022.06.029. Epub 2022 Jul 14.
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