During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversedproton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, atranslational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intra-cellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cellshave never been described in any other disease and now appear to be a specific hallmark of malignancy.As a consequence of this intracellular acid-base homeostatic failure, the attempt to induce cellular acidifi-cation using proton transport inhibitors and other intracellular acidifiers of different origins is becominga new therapeutic concept and selective target of cancer treatment, both as a metabolic mediator ofapoptosis and in the overcoming of multiple drug resistance (MDR). Importantly, there is increasing datashowing that different ion channels contribute to mediate significant aspects of cancer pH regulationand etiopathogenesis. Finally, we discuss the extension of this new pH-centric oncological paradigm intothe opposite metabolic and homeostatic acid-base situation found in human neurodegenerative diseases(HNDDs), which opens novel concepts in the prevention and treatment of HNDDs through the utilizationof a cohort of neural and non-neural derived hormones and human growth factors.

Cellular acidification as a new approach to cancer treatment and to the understanding and therapeutics of neurodegenerative diseases.

CARDONE, ROSA ANGELA;RESHKIN, Stephan Joel
2017-01-01

Abstract

During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversedproton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, atranslational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intra-cellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cellshave never been described in any other disease and now appear to be a specific hallmark of malignancy.As a consequence of this intracellular acid-base homeostatic failure, the attempt to induce cellular acidifi-cation using proton transport inhibitors and other intracellular acidifiers of different origins is becominga new therapeutic concept and selective target of cancer treatment, both as a metabolic mediator ofapoptosis and in the overcoming of multiple drug resistance (MDR). Importantly, there is increasing datashowing that different ion channels contribute to mediate significant aspects of cancer pH regulationand etiopathogenesis. Finally, we discuss the extension of this new pH-centric oncological paradigm intothe opposite metabolic and homeostatic acid-base situation found in human neurodegenerative diseases(HNDDs), which opens novel concepts in the prevention and treatment of HNDDs through the utilizationof a cohort of neural and non-neural derived hormones and human growth factors.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11586/182826
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