Review Article

粘贴。阻断前列腺癌脂质表型作为代谢治疗:一个理论建议

卷 31, 期 22, 2024

发表于: 09 August, 2023

页: [3265 - 3285] 页: 21

弟呕挨: 10.2174/0929867330666230607104441

价格: $65

摘要

背景:前列腺癌是112个国家中最常见的恶性肿瘤,也是18个国家中导致死亡的主要原因。除了继续研究预防和早期诊断之外,改进治疗方法并使其更加负担得起也是必不可少的。从这个意义上说,重新利用低成本和广泛可得的药物进行治疗,可以降低这种疾病的全球死亡率。由于其治疗意义,恶性代谢表型变得越来越重要。癌症通常以糖酵解、谷氨酰胺解和脂肪酸合成的过度激活为特征。然而,前列腺癌尤其具有脂质性;它在脂肪酸合成、胆固醇和脂肪酸氧化途径中表现出增强的活性(粮农组织)。 目的:基于文献回顾,我们提出PaSTe方案(泮托拉唑,辛伐他汀,曲美他嗪)作为前列腺癌的代谢治疗。泮托拉唑和辛伐他汀抑制脂肪酸合成酶(FASN)和3-羟基-3-甲基戊二酰辅酶A还原酶(HMGCR),从而分别阻断脂肪酸和胆固醇的合成。相反,曲美他嗪抑制酶3-β-酮酰基-辅酶a硫酶(3- kat),一种催化脂肪酸氧化的酶(FAO)。众所周知,这些酶的药理或基因缺失对前列腺癌具有抗肿瘤作用。 结果:基于这些信息,我们假设PaSTe方案将增加抗肿瘤效果,并可能阻碍代谢重编程转变。现有的知识表明,在这些药物的标准剂量下,酶抑制发生在血浆中达到的摩尔浓度。 结论:我们的结论是,由于其治疗前列腺癌的临床潜力,该方案值得进行临床前评估。

关键词: 前列腺癌,代谢阻断,抗癌药物再利用,新脂肪酸合成,甲羟戊酸途径,脂肪酸氧化。

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