An Innovative Approach to Understanding and Treating Cancer: Targeting pH - 1st Edition - ISBN: 9780128190593, 9780128190609

An Innovative Approach to Understanding and Treating Cancer: Targeting pH

1st Edition

From Etiopathogenesis to New Therapeutic Avenues

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Authors: Tomas Koltai Stephan Reshkin Salvador Harguindey
Paperback ISBN: 9780128190593
eBook ISBN: 9780128190609
Imprint: Academic Press
Published Date: 16th January 2020
Page Count: 574
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An Innovative Approach to Studying and Treating Cancer: Targeting pH describes one of the few characteristics of cancer that is not shared by normal tissues: the reversal or inversion of the pH gradient when intracellular pH becomes alkaline and extracellular pH becomes acid. This is now recognized as one of the most selective and differential hallmarks of all cancer cells and tissues, being the opposite of the condition found in normal tissues and a potential target in order to achieve either a stable disease or even regression with no toxicity.

The book discusses topics such as lactic acid and its transport system in the pH paradigm, mechanisms to decrease extra cellular pH and increase intracellular pH, NHE-1 activity in cancer, carbonic anhydrases, vacuolar ATPase proton pump, and the sodium-bicarbonate cotransporter system. Additionally, it discusses complementary pharmacological interventions, cellular acidification and extracellular alkalinization as a new and integral approach to cancer treatment.

Key Features

  • Analyzes the mechanisms that lead to the inversion of pH gradient in cancer tissues
  • Summarizes almost 100 years of research on pH inversion in cancer in one single source, discussing the most relevant and updated researches in the field
  • Proposes new efficient treatments against cancer using pH inversion mechanisms, either with new drugs like proton transport inhibitors and proton pump inhibitors (PTIs and PPIs) or with repurposed drugs


Oncologists; cancer researchers; graduate students; molecular biologists

Table of Contents

PART 1: Metabolism and pH physiopathology of cancer
1. Introduction
2. Cancer metabolism
3. The pH alterations in cancer: causes and consequences
4. Lactic acid and its transport system
5. The sodium hydrogen exchanger
6. The voltage gated sodium channels
7. Carbonic anhydrases
8. Proton pumps
9. The sodium/bicarbonate co-transporter
10. Aquaporins
11. Invadopodia and the migration/invasion process
12. The Sp1 transcription factor

PART 1: Therapeutics
13. Pharmacological interventions – Part I
14. Pharmacological interventions – Part II
15. Pharmacological interventions – Part III
16. Pharmacological interventions – Part IV
17. Therapeutics: the scheme
18. Therapeutics: ancillary treatments
19. Preventing metastasis
20. Proton inhibitors in pets’ cancer
21. pH-related nanoparticles in cancer treatment
22. Conclusions and future perspectives


No. of pages:
© Academic Press 2020
16th January 2020
Academic Press
Paperback ISBN:
eBook ISBN:

About the Author

Tomas Koltai

Graduated as MD at University of Buenos Aires School of Medicine, Argentina (1969). Surgical Intern, Nassau County Medical Center, USA (1972-73) and Surgical Resident, at the same institution (1973-1975). Board Certified Specialist in Medical Oncology (1985). PhD in Chemistry (1997) and Master in Sciences in Molecular Oncology, University of Buenos Aires (2011). Staff oncologist, Sanatorio Mater Dei, Argentina (1985-1990). Head of Oncology, Central Hospital of the Centro Gallego de Buenos Aires (1990-2000) and Medical Director, at the same institution (2000-2002). Head of the Department of Chemotherapy, National Social Services for Retirees, Argentina (2002-2014). Head of the Department of Oncology, Social Services of the National Food Workers Union, Argentina (2010-2014) and Medical Director at the same institution (2014-2016). He has authored several seminal publications on pH and cancer and created the new “triple- edged cancer treatment”.

Affiliations and Expertise

Clinical Collaborator, Institute for Clinical Biology and Metabolism

Stephan Reshkin

Professor Reshkin has a long-standing expertise in the biology of the NHE1 system and has extensively investigated its role in tumor transformation and malignancy resulting in more than 40 publications on just that topic. Last year he was a guest author and editor together with Salvador Harguindey on a special issue in Seminars in Cancer Biology concerning the role of pH in cancer and neurodegeneration. Recently his group has provided a structural basis for this role of the NHE1 in tumor cell invasion and the regulation of proteolytic activity localized at invadopodia. To do this, the Reshkin group has developed a series of innovative techniques to study the dynamics of invadopodia.

Affiliations and Expertise

Associate Professor, Department of Bioscience, Biotechnology and Biopharmaceutics, University of Bari, Italy

Salvador Harguindey

Specialty in Medical Endocrinology, Royal Infirmary Hospital, University of Edinburgh, Scotland (1974-1977) and Department of Endocrinology, Eugene Taldmage Memorial Hospital, USA (1977-1981). Specialty in Medical Oncology, Roswell Park Memorial Institute, USA (1981-1985). Consultant in Medical Oncologist, University Clinic, Spain ( 1985-2000). He co-founded and was Vice-president of the International Society for Proton Dynamics of Cancer (ISPDC) (2008). Co-editor and author on a special issue in Seminars in Cancer Biology (2017) entitled “The new pH-centric anticancer paradigm in Oncology and Medicine”. Harguindey has published more than 140 scientific publications on a new and integral approach to the understanding of cancer and neurodegenerative diseases based upon hydrogen ion dynamics, from etiopathogenesis to treatment, that he originally and singlehandedly created.

Affiliations and Expertise

Director, Institute for Clinical Biology and Metabolism, Vitoria, Spain

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