以二氯乙酸盐为基础的代谢性癌症治疗的15年发展:病例报告综述

Akbar Khan, M. Ghen
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引用次数: 0

摘要

尽管Otto Warburg在20世纪20年代发现了癌细胞的有氧糖酵解,但开发针对癌细胞代谢的治疗方法的潜力基本上被忽视了,直到2007年,一组加拿大研究人员发表了一篇开创性的论文。Bonnet等人(矛盾的是,他们不是肿瘤学专家)发现,仿制药二氯乙酸钠(“DCA”)可以在体外和体内逆转癌细胞的Warburg表型,导致大鼠的自然癌细胞自杀和肿瘤缩小。这种现象以前被认为是不可能的,因为人们认为恶性细胞中的线粒体被永久改变,无法引发细胞凋亡。尽管DCA作为癌症治疗的大型临床试验尚未完成,但北美和欧洲的少数医生通过独立的观察研究和创造性思维,迅速将这一新知识转化为临床癌症方案。由于大多数司法管辖区允许超说明书用药,临床医生最初开始在所有常规治疗失败的患者中使用DCA。近年来,DCA的新的抗癌机制被发现,如抑制血管生成、免疫激活和靶向肿瘤干细胞等。2011年前后,Seyfried (USA)的工作开始阐明谷氨酰胺抑制的重要性,并提出多能靶向方法优于单独的糖酵解抑制。作者将塞弗里德的概念结合起来,共同努力创造了一种新的代谢方案,名为“MOMENTUM”(代谢、肿瘤、多能靶向、通用、改良)。在这个方案中,葡萄糖和谷氨酰胺代谢是同时靶向多种天然和药物药物静脉注射的组合。在几个困难的癌症病例中令人惊讶的初步临床结果证实,代谢多靶向方法非常有希望,而且比代谢单一疗法更有希望。这种治疗癌症的方法几乎不存在危及生命的副作用,治疗费用也在可控范围内。令人失望的是,大型临床试验缺乏行业资金支持,但这并没有阻碍代谢疗法作为一种临床可行方法的发展,这证明了纯粹的医学科学可以征服持续推动的数十亿美元的经济回报。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
A 15 Year Evolution of Dichloroacetate-Based Metabolic Cancer Therapy: A Review with Case Reports
Despite Otto Warburg’s discovery of aerobic glycolysis in cancer cells in the 1920’s, the potential for developing therapeutics that targeted cancer cell metabolism was essentially ignored until 2007 when a groundbreaking publication was released from a group of Canadian researchers. Bonnet et al. (who paradoxically were not specialized in oncology) discovered that the generic drug dichloroacetate sodium (“DCA”) could reverse the Warburg phenotype in cancer cells in vitro and in vivo resulting in natural cancer cell suicide and tumour shrinkage in rats. This phenomenon was previously thought to be impossible as it was believed that mitochondria in malignant cells were permanently altered and unable to trigger apoptosis. Despite the fact that no large clinical trial of DCA as a cancer therapy was ever completed, a small number of doctors in North America and Europe rapidly translated this new knowledge into clinical cancer protocols through independent observational research and creative thinking. Since off-label drug use is permitted in most jurisdictions, clinicians initially began to use DCA in patients who had failed all conventional therapies. Over the years, further novel anti-cancer mechanisms of DCA were discovered such as angiogenesis inhibition, immune activation and cancer stem cell targeting. Around 2011, the work of Seyfried (USA) began to illuminate the importance of glutamine inhibition and suggested that a multi-energetic targeted approach was superior to glycolysis inhibition alone. A collaborative effort of the authors incorporating Seyfried’s concepts resulted in the creation of a new metabolic protocol named “MOMENTUM” (Metabolic, Oncologic, Multi-ENergetic Targeted, Universal, Modified). In this protocol, glucose and glutamine metabolism were targeted simultaneously with a combination of multiple natural and pharmacologic agents administered intravenously. Surprising preliminary clinical results in several difficult cancer cases confirmed that metabolic multi-targeted methods are extremely promising, and more so than metabolic monotherapy. Life threatening side effects of this approach to cancer management are virtually non-existent and therapy costs are manageable. A disappointing absence of industry funding for large clinical trials has not curtailed the development of the metabolic approach as a clinically viable methodology, proving that unadulterated medical science can conquer the ongoing push for multibillion-dollar economic reward.
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