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1.
Int J Mol Sci ; 21(3)2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32046158

RESUMO

Despite all efforts, the treatment of breast cancer (BC) cannot be considered to be a success story. The advances in surgery, chemotherapy and radiotherapy have not been sufficient at all. Indeed, the accumulated experience clearly indicates that new perspectives and non-main stream approaches are needed to better characterize the etiopathogenesis and treatment of this disease. This contribution deals with how the new pH-centric anticancer paradigm plays a fundamental role in reaching a more integral understanding of the etiology, pathogenesis, and treatment of this multifactorial disease. For the first time, the armamentarium available for the treatment of the different types and phases of BC is approached here from a Unitarian perspective-based upon the hydrogen ion dynamics of cancer. The wide-ranged pH-related molecular, biochemical and metabolic model is able to embrace most of the fields and subfields of breast cancer etiopathogenesis and treatment. This single and integrated approach allows advancing towards a unidirectional, concerted and synergistic program of treatment. Further efforts in this line are likely to first improve the therapeutics of each subtype of this tumor and every individual patient in every phase of the disease.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/metabolismo , Inibidores da Bomba de Prótons/uso terapêutico , Prótons , Animais , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Bombas de Próton/metabolismo , Microambiente Tumoral
2.
Semin Cancer Biol ; 43: 157-179, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28193528

RESUMO

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.


Assuntos
Ácidos/metabolismo , Doenças Neurodegenerativas/terapia , Apoptose , Humanos , Concentração de Íons de Hidrogênio , Doenças Neurodegenerativas/metabolismo
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