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

Harguindey, Salvador; Stanciu, Daniel; Devesa, Jes�s; Alfarouk, Khalid; Cardone, Rosa Angela; Polo Orozco, Julian David; Devesa, Pablo; Rauch, Cyril; Orive, Gorka; Anitua, Eduardo; Roger, S�bastien; Reshkin, Stephan J.

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Salvador Harguindey

Daniel Stanciu

Jes�s Devesa

Khalid Alfarouk

Rosa Angela Cardone

Julian David Polo Orozco

Pablo Devesa

Associate Professor

Gorka Orive

Eduardo Anitua

S�bastien Roger

Stephan J. Reshkin


During the last few years, the understanding of the dysregulated hydrogen ion dynamics and reversed proton gradient of cancer cells has resulted in a new and integral pH-centric paradigm in oncology, a translational model embracing from cancer etiopathogenesis to treatment. The abnormalities of intracellular alkalinization along with extracellular acidification of all types of solid tumors and leukemic cells have 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 acidification using proton transport inhibitors and other intracellular acidifiers of different origins is becoming a new therapeutic concept and selective target of cancer treatment, both as a metabolic mediator of apoptosis and in the overcoming of multiple drug resistance (MDR). Importantly, there is increasing data showing that different ion channels contribute to mediate significant aspects of cancer pH regulation and etiopathogenesis. Finally, we discuss the extension of this new pH-centric oncological paradigm into the 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 utilization of a cohort of neural and non-neural derived hormones and human growth factors.

Journal Article Type Article
Acceptance Date Feb 11, 2017
Online Publication Date Feb 11, 2017
Publication Date Apr 30, 2017
Deposit Date Jun 20, 2017
Publicly Available Date Jun 20, 2017
Journal Seminars in Cancer Biology
Print ISSN 1044-579X
Electronic ISSN 1096-3650
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 43
Keywords Cellular acidification in cancer treatment; Cellular acidifiers; pH, NHE, cancer and neurodegenerative diseases;
Ion channels in cancer and neurodegeneration;
Growth factors in cancer and neurodegenerative diseases
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