选择性氨基酸限制疗法(SAART):一种针对所有类型癌细胞的非药物策略

M. López-Lázaro
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引用次数: 13

摘要

在我们开发出高度选择性的抗癌疗法之前,转移将继续是大多数患者无法治愈的疾病。这些疗法的发展需要发现和利用癌细胞和正常细胞之间的主要差异。尽管癌细胞的许多DNA变化的总和构成了如此重大的差异,但目前还没有办法将这些变化作为一个整体加以利用。在这里,我提出了一种非药物策略,通过利用其完整的DNA改变来选择性地杀死任何类型的癌细胞,包括癌症干细胞。它的基础是创造具有挑战性的环境条件,只有dna未受损的细胞才能克服这些条件。细胞生存需要持续的蛋白质合成,而这又需要足够的20种氨基酸(AAs)。如果我们暂时限制特定的AAs,并保持其他缺陷触发蛋白水解的高水平,我们将迫使细胞激活各种遗传程序,以获得20种蛋白原AAs中的每一种的足够水平。由于癌细胞的DNA在特定的环境条件下发生了极大的变化,因此它们可能无法激活适应新环境并在新环境中生存所需的遗传程序。癌症患者可以通过无蛋白质的人工饮食成功治疗,其中特定AAs的水平被控制。讨论了测试和实施这种廉价和普遍的抗癌策略的实际考虑。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Selective amino acid restriction therapy (SAART): a non-pharmacological strategy against all types of cancer cells
Metastasis will continue to be an incurable disease for most patients until we develop highly selective anticancer therapies. The development of these therapies requires finding and exploiting major differences between cancer cells and normal cells. Although the sum of the many DNA alterations of cancer cells makes up such a major difference, there is currently no way of exploiting these alterations as a whole. Here I propose a non-pharmacological strategy to selectively kill any type of cancer cell, including cancer stem cells, by exploiting their complete set of DNA alterations. It is based on creating challenging environmental conditions that only cells with undamaged DNAs can overcome. Cell survival requires continuous protein synthesis, which in turn requires adequate levels of 20 amino acids (AAs). If we temporarily restrict specific AAs and keep high levels of others whose deficit triggers proteolysis, we will force cells to activate a variety of genetic programs to obtain adequate levels of each of the 20 proteinogenic AAs. Because cancer cells have an extremely altered DNA that has evolved under particular environmental conditions, they may be unable to activate the genetic programs required to adapt to and survive the new environment. Cancer patients may be successfully treated with a protein-free artificial diet in which the levels of specific AAs are manipulated. Practical considerations for testing and implementing this cheap and universal anticancer strategy are discussed.
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