A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics

Abstract

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.

Towards An Integral Therapeutic Protocol for Breast Cancer based upon the New H+-Centered Anticancer Paradigm of the Late Post-Warburg Era

“…A similar protumoral effect have certain oncogenes, gene mutations and products like BRCA1 and BRCA2, apart from a dysfunctional p53 [65] and certain chemicals known to play a role in carcinogenesis [66,67]. All this myriad of factors belong to an already large list of mediating causes of cancer and BC cancer previously reported [9,10].…”

“…Since Peter Mitchell seminal description of the chemiosmotic hypothesis, this main energy-yielding mechanism dealing with electron transport and ATP synthesis in nature can also be considered as another acid-base mechanism induced by a H+ gradient across the mitochondrial membrane, a phenomenon dependent of ATPases [83]. From then on, it was going to elapse a long time until BC could also be considered a molecular, biochemical and metabolic disease of an intimate acid-base nature [10]. As it generally happens with PTs, V-ATPase proton pumps (PPs) are highly expressed in many tumors, apart from in BC, following the same rule of PTs, namely, that their upregulation is a sign of bad prognosis, facilitating faster cancer growth, tissue invasion, the metastatic process and chemoresistance (MDR), either in BC or other malignant tumors [84][85][86].…”

“…High glucose loads, with or without insulin, also stimulate Na + /H + activity, cell cycle progression and activation of oncogene expression [133]. These effects are associated with BC carcinogenicity and progression [10], justifying the fact that hyperinsulinemia and obesity are protumoral factors that increase the incidence of BC [134][135][136]. On the contrary, antidiabetic drugs of the sulfonylurea family, known to stimulate the pancreatic secretion of INS, appear to have a negative impact on BC growth, also increasing BC risk [137][138][139].…”

“…Under this perspective our group has recently published two conceptual publications, one on the pHrelated etiopathogenesis and treatment of brain tumors [9], and a second one on breast cancer [10].…”

The Interplay of Dysregulated pH and Electrolyte Imbalance in Cancer

“…The pH dysregulation observed in cancer cells helps to drive tumor processes, which are highly sensitive to even minimum pHi variations: these are cancer initiation, progression, adaptation, proliferation, migration, and the programming and reprogramming of tumor cell metabolism [14,[123][124][125][126][127]. Furthermore, many effects on biologic processes of a cell are generated as a result of pH-sensitive functions such as the regulation of protein expression, the affinity of proteins to bind with a ligand as well as the activity of ion channels/enzymes [124,128].…”