Koltai Tomas
Centro de Diagnostico y Tratamiento de la Obra Social del Personal de la Alimentacion, Talar de Pacheco, Buenos Aires 1617, Argentina.
Int J Mol Sci. 2020 Dec 3;21(23):9221. doi: 10.3390/ijms21239221.
The inversion of the pH gradient in malignant tumors, known as the pH paradigm, is increasingly becoming accepted by the scientific community as a hallmark of cancer. Accumulated evidence shows that this is not simply a metabolic consequence of a dysregulated behavior, but rather an essential process in the physiopathology of accelerated proliferation and invasion. From the over-simplification of increased lactate production as the cause of the paradigm, as initially proposed, basic science researchers have arrived at highly complex and far-reaching knowledge, that substantially modified that initial belief. These new developments show that the paradigm entails a different regulation of membrane transporters, electrolyte exchangers, cellular and membrane enzymes, water trafficking, specialized membrane structures, transcription factors, and metabolic changes that go far beyond fermentative glycolysis. This complex world of dysregulations is still shuttered behind the walls of experimental laboratories and has not yet reached bedside medicine. However, there are many known pharmaceuticals and nutraceuticals that are capable of targeting the pH paradigm. Most of these products are well known, have low toxicity, and are also inexpensive. They need to be repurposed, and this would entail shorter clinical studies and enormous cost savings if we compare them with the time and expense required for the development of a new molecule. Will targeting the pH paradigm solve the "cancer problem"? Absolutely not. However, reversing the pH inversion would strongly enhance standard treatments, rendering them more efficient, and in some cases permitting lower doses of toxic drugs. This article's goal is to describe how to reverse the pH gradient inversion with existing drugs and nutraceuticals that can easily be used in bedside medicine, without adding toxicity to established treatments. It also aims at increasing awareness among practicing physicians that targeting the pH paradigm would be able to improve the results of standard therapies. Some clinical cases will be presented as well, showing how the pH gradient inversion can be treated at the bedside in a simple manner with repurposed drugs.
恶性肿瘤中pH梯度的反转，即所谓的pH模式，正日益被科学界接受为癌症的一个标志。越来越多的证据表明，这不仅仅是行为失调的代谢后果，而是加速增殖和侵袭的生理病理学中的一个关键过程。最初有人提出，该模式的原因是乳酸生成增加，但这种过于简单的观点已被基础科学研究人员深入且复杂的知识所修正，这些知识极大地改变了最初的认知。这些新进展表明，该模式涉及对膜转运蛋白、电解质交换器、细胞和膜酶、水运输、特殊膜结构、转录因子以及远超发酵性糖酵解的代谢变化的不同调节。这个失调的复杂世界仍被局限在实验室的围墙之内，尚未应用于临床医疗。然而，有许多已知的药物和营养保健品能够针对pH模式发挥作用。这些产品大多广为人知，毒性低，价格也便宜。它们需要被重新定位用途，如果与开发一种新分子所需的时间和费用相比，这将意味着更短的临床研究和巨大的成本节约。针对pH模式能解决“癌症问题”吗？绝对不能。然而，逆转pH反转将有力地增强标准治疗方法，使其更有效，并且在某些情况下允许降低有毒药物的剂量。本文的目的是描述如何用现有的、可轻易应用于临床医疗且不会给既定治疗增加毒性的药物和营养保健品来逆转pH梯度反转。它还旨在提高执业医师的认识，即针对pH模式能够改善标准疗法的效果。本文还将展示一些临床病例，说明如何用重新定位用途的药物在床边以简单的方式治疗pH梯度反转。
