An Innovative Approach to Understanding and Treating Cancer: Targeting pH: From Etiopathogenesis to New Therapeutic Avenues

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.

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 fieldProposes 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

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