Analyze Diet
Journal of experimental & clinical cancer research : CR2015; 34(1); 93; doi: 10.1186/s13046-015-0204-z

Proton pump inhibitors for the treatment of cancer in companion animals.

Abstract: The treatment of cancer presents a clinical challenge both in human and veterinary medicine. Chemotherapy protocols require the use of toxic drugs that are not always specific, do not selectively target cancerous cells thus resulting in many side effects. A recent therapeutic approach takes advantage of the altered acidity of the tumour microenvironment by using proton pump inhibitors (PPIs) to block the hydrogen transport out of the cell. The alteration of the extracellular pH kills tumour cells, reverses drug resistance, and reduces cancer metastasis. Human clinical trials have prompted to consider this as a viable and safe option for the treatment of cancer in companion animals. Preliminary animal studies suggest that the same positive outcome could be achievable. The purpose of this review is to support investigations into the use of PPIs for cancer treatment cancer in companion animals by considering the evidence available in both human and veterinary medicine.
Publication Date: 2015-09-04 PubMed ID: 26337905PubMed Central: PMC4559889DOI: 10.1186/s13046-015-0204-zGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research article explores the potential of proton pump inhibitors (PPIs) for treating cancer in pets, using evidence from both human and veterinary medicine. PPIs affect the acidity of the cancerous environment, which can kill tumor cells, improve medicinal effectiveness, and reduce the spread of cancer.

Understanding Proton Pump Inhibitors (PPIs)

  • Proton pump inhibitors (PPIs) are a class of drugs primarily used to treat gastrointestinal disorders such as ulcers and gastroesophageal reflux disease.
  • These drugs function by reducing the production of stomach acid, which in turn helps to alleviate symptoms of these disorders.
  • However, recent research has suggested that they may also have cancer-fighting properties.

The Role of PPIs in Cancer Treatment

  • Cancer treatment often involves the use of chemotherapy, which unfortunately does not selectively target cancer cells and can result in numerous adverse side effects.
  • It has been discovered that cancerous cells often have an altered acidity – a trait that PPIs can potentially exploit to target these cells specifically.
  • By using PPIs, it’s possible to block the transport of hydrogen out of the cancer cell, which alters the extracellular pH levels. This alteration can lead to the death of tumor cells, a reduction in the resistance to drugs, and decreased cancer metastasis.

Potential for PPIs in Veterinary Medicine

  • The results derived from human clinical trials suggest the potential viability of PPIs as a treatment option for cancer in companion animals.
  • There have been preliminary studies conducted in animals that support this assertion, however the results are still early-stage and require further validation.
  • Use of PPIs in treating cancer in pets is a relatively novel approach, and extensive research is needed to fully understand its efficacy, safety, and best practices.
  • The aim of this review is to stimulate further research into the use of PPIs for cancer treatment in companion animals, stressing the importance of examining the existing available evidence in both human and veterinary medicine.

Cite This Article

APA
Walsh M, Fais S, Spugnini EP, Harguindey S, Abu Izneid T, Scacco L, Williams P, Allegrucci C, Rauch C, Omran Z. (2015). Proton pump inhibitors for the treatment of cancer in companion animals. J Exp Clin Cancer Res, 34(1), 93. https://doi.org/10.1186/s13046-015-0204-z

Publication

ISSN: 1756-9966
NlmUniqueID: 8308647
Country: England
Language: English
Volume: 34
Issue: 1
Pages: 93
PII: 93

Researcher Affiliations

Walsh, Megan
  • School of Veterinary Medicine and Science, University of Nottingham, College Road, Sutton Bonington, LE12 5RD, UK. Megan.walsh@nottingham.ac.uk.
Fais, Stefano
  • Department of Therapeutic Research and Medicines Evaluation, National Institute of Health, Viale Regina Elena 299, 00161, Rome, Italy. stefano.fais@iss.it.
Spugnini, Enrico Pierluigi
  • SAFU, Regina Elena Cancer Institute, Via delle Messi d' Oro 156, Rome, Italy. spugnini.vet@tiscali.it.
Harguindey, Salvador
  • Institute for Clinical Biology and Metabolism, c) Postas 13, 01004, Vitoria, Spain. salvaszh@telefonica.net.
Abu Izneid, Tareq
  • College of Pharmacy, Umm Al-Qura University, Al-Abidiyya, 21955, Makkah, Kingdom of Saudi Arabia. tmabuzneid@uqu.edu.sa.
Scacco, Licia
  • Equivet Roma Hospital, Equine Veterinary Clinic, Via di Torre di Sant'Anastasia 83, 00134, Rome, Italy.
Williams, Paula
  • School of Veterinary Medicine and Science, University of Nottingham, College Road, Sutton Bonington, LE12 5RD, UK. paula.williams@nottingham.ac.uk.
Allegrucci, Cinzia
  • School of Veterinary Medicine and Science, University of Nottingham, College Road, Sutton Bonington, LE12 5RD, UK. cinzia.allegrucci@nottingham.ac.uk.
Rauch, Cyril
  • School of Veterinary Medicine and Science, University of Nottingham, College Road, Sutton Bonington, LE12 5RD, UK. cyril.rauch@nottingham.ac.uk.
Omran, Ziad
  • College of Pharmacy, Umm Al-Qura University, Al-Abidiyya, 21955, Makkah, Kingdom of Saudi Arabia. zhomran@uqu.edu.sa.

MeSH Terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Dog Diseases / drug therapy
  • Dog Diseases / pathology
  • Dogs
  • Drug Resistance, Neoplasm
  • Horse Diseases / drug therapy
  • Horse Diseases / pathology
  • Horses
  • Humans
  • Hydrogen-Ion Concentration
  • Neoplasms / drug therapy
  • Neoplasms / pathology
  • Neoplasms / veterinary
  • Pets
  • Proton Pump Inhibitors / pharmacology
  • Proton Pump Inhibitors / therapeutic use

References

This article includes 54 references
  1. De Milito A, Fais S. Tumor acidity, chemoresistance and proton pump inhibitors.. Future Oncol 2005 Dec;1(6):779-86.
    doi: 10.2217/14796694.1.6.779pubmed: 16556057google scholar: lookup
  2. Howlader N NA, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z,Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (2013) http://seer.cancer.gov/csr/1975_2012/.
  3. Martínez-Zaguilán R, Raghunand N, Lynch RM, Bellamy W, Martinez GM, Rojas B, Smith D, Dalton WS, Gillies RJ. pH and drug resistance. I. Functional expression of plasmalemmal V-type H+-ATPase in drug-resistant human breast carcinoma cell lines.. Biochem Pharmacol 1999 May 1;57(9):1037-46.
    pubmed: 10796074doi: 10.1016/s0006-2952(99)00022-2google scholar: lookup
  4. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation.. Cell 2011 Mar 4;144(5):646-74.
    doi: 10.1016/j.cell.2011.02.013pubmed: 21376230google scholar: lookup
  5. De Milito A, Marino ML, Fais S. A rationale for the use of proton pump inhibitors as antineoplastic agents.. Curr Pharm Des 2012;18(10):1395-406.
    doi: 10.2174/138161212799504911pubmed: 22360553google scholar: lookup
  6. Mérida I, Avila-Flores A. Tumor metabolism: new opportunities for cancer therapy.. Clin Transl Oncol 2006 Oct;8(10):711-6.
    doi: 10.1007/s12094-006-0117-6pubmed: 17074669google scholar: lookup
  7. Xu RH, Pelicano H, Zhou Y, Carew JS, Feng L, Bhalla KN, Keating MJ, Huang P. Inhibition of glycolysis in cancer cells: a novel strategy to overcome drug resistance associated with mitochondrial respiratory defect and hypoxia.. Cancer Res 2005 Jan 15;65(2):613-21.
    pubmed: 15695406
  8. WARBURG O. On the origin of cancer cells.. Science 1956 Feb 24;123(3191):309-14.
    doi: 10.1126/science.123.3191.309pubmed: 13298683google scholar: lookup
  9. Mahon BP, Pinard MA, McKenna R. Targeting carbonic anhydrase IX activity and expression.. Molecules 2015 Jan 30;20(2):2323-48.
    doi: 10.3390/molecules20022323pmc: PMC6272707pubmed: 25647573google scholar: lookup
  10. Kennedy KM, Dewhirst MW. Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation.. Future Oncol 2010 Jan;6(1):127-48.
    doi: 10.2217/fon.09.145pmc: PMC2819205pubmed: 20021214google scholar: lookup
  11. Demaurex N. pH Homeostasis of cellular organelles.. News Physiol Sci 2002 Feb;17:1-5.
  12. Alexander SP, Mathie A, Peters JA. Guide to Receptors and Channels (GRAC), 5th edition.. Br J Pharmacol 2011 Nov;164 Suppl 1(Suppl 1):S1-324.
  13. Nakamura S. Handbook of H + −ATPases. 2014. Pan Stanford. CRC Press, Taylor & Francis Group, UK
  14. Slepkov ER, Rainey JK, Sykes BD, Fliegel L. Structural and functional analysis of the Na+/H+ exchanger.. Biochem J 2007 Feb 1;401(3):623-33.
    doi: 10.1042/BJ20061062pmc: PMC1770851pubmed: 17209804google scholar: lookup
  15. Ferrari S, Perut F, Fagioli F, Brach Del Prever A, Meazza C, Parafioriti A, Picci P, Gambarotti M, Avnet S, Baldini N, Fais S. Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed.. J Transl Med 2013 Oct 24;11:268.
    pmc: PMC3815282pubmed: 24156349doi: 10.1186/1479-5876-11-268google scholar: lookup
  16. Iessi EMM, Lozupone F, Fais S, De Milito A. Tumor acidity and malignancy: novel aspects in the design of anti-tumor therapy.. Cancer Therapy 2008;6:55–66.
  17. Rauch C. Toward a mechanical control of drug delivery. On the relationship between Lipinski's 2nd rule and cytosolic pH changes in doxorubicin resistance levels in cancer cells: a comparison to published data.. Eur Biophys J 2009 Sep;38(7):829-46.
    doi: 10.1007/s00249-009-0429-xpubmed: 19296096google scholar: lookup
  18. Panagiotopoulou V, Richardson G, Jensen OE, Rauch C. On a biophysical and mathematical model of Pgp-mediated multidrug resistance: understanding the "space-time" dimension of MDR.. Eur Biophys J 2010 Jan;39(2):201-11.
    doi: 10.1007/s00249-009-0555-5pubmed: 19888571google scholar: lookup
  19. Daniel C, Bell C, Burton C, Harguindey S, Reshkin SJ, Rauch C. The role of proton dynamics in the development and maintenance of multidrug resistance in cancer.. Biochim Biophys Acta 2013 May;1832(5):606-17.
    doi: 10.1016/j.bbadis.2013.01.020pubmed: 23376112google scholar: lookup
  20. Calcinotto A, Filipazzi P, Grioni M, Iero M, De Milito A, Ricupito A, Cova A, Canese R, Jachetti E, Rossetti M, Huber V, Parmiani G, Generoso L, Santinami M, Borghi M, Fais S, Bellone M, Rivoltini L. Modulation of microenvironment acidity reverses anergy in human and murine tumor-infiltrating T lymphocytes.. Cancer Res 2012 Jun 1;72(11):2746-56.
    pubmed: 22593198doi: 10.1158/0008-5472.can-11-1272google scholar: lookup
  21. Harguindey S, Orive G, Luis Pedraz J, Paradiso A, Reshkin SJ. The role of pH dynamics and the Na+/H+ antiporter in the etiopathogenesis and treatment of cancer. Two faces of the same coin--one single nature.. Biochim Biophys Acta 2005 Sep 25;1756(1):1-24.
    pubmed: 16099110doi: 10.1016/j.bbcan.2005.06.004google scholar: lookup
  22. Sennoune SR, Bakunts K, Martínez GM, Chua-Tuan JL, Kebir Y, Attaya MN, Martínez-Zaguilán R. Vacuolar H+-ATPase in human breast cancer cells with distinct metastatic potential: distribution and functional activity.. Am J Physiol Cell Physiol 2004 Jun;286(6):C1443-52.
    pubmed: 14761893doi: 10.1152/ajpcell.00407.2003google scholar: lookup
  23. Fais S. Proton pump inhibitor-induced tumour cell death by inhibition of a detoxification mechanism.. J Intern Med 2010 May;267(5):515-25.
  24. Luciani F, Spada M, De Milito A, Molinari A, Rivoltini L, Montinaro A, Marra M, Lugini L, Logozzi M, Lozupone F, Federici C, Iessi E, Parmiani G, Arancia G, Belardelli F, Fais S. Effect of proton pump inhibitor pretreatment on resistance of solid tumors to cytotoxic drugs.. J Natl Cancer Inst 2004 Nov 17;96(22):1702-13.
    pubmed: 15547183doi: 10.1093/jnci/djh305google scholar: lookup
  25. Harguindey S, Arranz JL, Polo Orozco JD, Rauch C, Fais S, Cardone RA, Reshkin SJ. Cariporide and other new and powerful NHE1 inhibitors as potentially selective anticancer drugs--an integral molecular/biochemical/metabolic/clinical approach after one hundred years of cancer research.. J Transl Med 2013 Nov 6;11:282.
    pmc: PMC3826530pubmed: 24195657doi: 10.1186/1479-5876-11-282google scholar: lookup
  26. Harguindey S, Arranz JL, Wahl ML, Orive G, Reshkin SJ. Proton transport inhibitors as potentially selective anticancer drugs.. Anticancer Res 2009 Jun;29(6):2127-36.
    pubmed: 19528473
  27. Nakashima S, Hiraku Y, Tada-Oikawa S, Hishita T, Gabazza EC, Tamaki S, Imoto I, Adachi Y, Kawanishi S. Vacuolar H+-ATPase inhibitor induces apoptosis via lysosomal dysfunction in the human gastric cancer cell line MKN-1.. J Biochem 2003 Sep;134(3):359-64.
    pubmed: 14561721doi: 10.1093/jb/mvg153google scholar: lookup
  28. McCarty MF, Whitaker J. Manipulating tumor acidification as a cancer treatment strategy.. Altern Med Rev 2010 Sep;15(3):264-72.
    pubmed: 21155627
  29. Matthews H, Ranson M, Kelso MJ. Anti-tumour/metastasis effects of the potassium-sparing diuretic amiloride: an orally active anti-cancer drug waiting for its call-of-duty?. Int J Cancer 2011 Nov 1;129(9):2051-61.
    doi: 10.1002/ijc.26156pubmed: 21544803google scholar: lookup
  30. Mattsson JP, Väänänen K, Wallmark B, Lorentzon P. Omeprazole and bafilomycin, two proton pump inhibitors: differentiation of their effects on gastric, kidney and bone H(+)-translocating ATPases.. Biochim Biophys Acta 1991 Jun 18;1065(2):261-8.
    doi: 10.1016/0005-2736(91)90238-4pubmed: 1647821google scholar: lookup
  31. Moriyama Y, Patel V, Ueda I, Futai M. Evidence for a common binding site for omeprazole and N-ethylmaleimide in subunit A of chromaffin granule vacuolar-type H(+)-ATPase.. Biochem Biophys Res Commun 1993 Oct 29;196(2):699-706.
    doi: 10.1006/bbrc.1993.2306pubmed: 8240346google scholar: lookup
  32. Parks SK, Chiche J, Pouysségur J. Disrupting proton dynamics and energy metabolism for cancer therapy.. Nat Rev Cancer 2013 Sep;13(9):611-23.
    doi: 10.1038/nrc3579pubmed: 23969692google scholar: lookup
  33. De Milito A, Iessi E, Logozzi M, Lozupone F, Spada M, Marino ML, Federici C, Perdicchio M, Matarrese P, Lugini L, Nilsson A, Fais S. Proton pump inhibitors induce apoptosis of human B-cell tumors through a caspase-independent mechanism involving reactive oxygen species.. Cancer Res 2007 Jun 1;67(11):5408-17.
    pubmed: 17545622doi: 10.1158/0008-5472.can-06-4095google scholar: lookup
  34. Thomson AB, Sauve MD, Kassam N, Kamitakahara H. Safety of the long-term use of proton pump inhibitors.. World J Gastroenterol 2010 May 21;16(19):2323-30.
    doi: 10.3748/wjg.v16.i19.2323pmc: PMC2874135pubmed: 20480516google scholar: lookup
  35. Shin JM, Sachs G. Pharmacology of proton pump inhibitors.. Curr Gastroenterol Rep 2008 Dec;10(6):528-34.
    doi: 10.1007/s11894-008-0098-4pmc: PMC2855237pubmed: 19006606google scholar: lookup
  36. Wallmark B, Brändström A, Larsson H. Evidence for acid-induced transformation of omeprazole into an active inhibitor of (H+ + K+)-ATPase within the parietal cell.. Biochim Biophys Acta 1984 Dec 19;778(3):549-58.
    doi: 10.1016/0005-2736(84)90406-1pubmed: 6095911google scholar: lookup
  37. Shin JM, Cho YM, Sachs G. Chemistry of covalent inhibition of the gastric (H+, K+)-ATPase by proton pump inhibitors.. J Am Chem Soc 2004 Jun 30;126(25):7800-11.
    doi: 10.1021/ja049607wpubmed: 15212527google scholar: lookup
  38. Shin JM, Kim N. Pharmacokinetics and pharmacodynamics of the proton pump inhibitors.. J Neurogastroenterol Motil 2013 Jan;19(1):25-35.
    doi: 10.5056/jnm.2013.19.1.25pmc: PMC3548122pubmed: 23350044google scholar: lookup
  39. Marino ML, Fais S, Djavaheri-Mergny M, Villa A, Meschini S, Lozupone F, Venturi G, Della Mina P, Pattingre S, Rivoltini L, Codogno P, De Milito A. Proton pump inhibition induces autophagy as a survival mechanism following oxidative stress in human melanoma cells.. Cell Death Dis 2010 Oct 21;1(10):e87.
    pmc: PMC3035900pubmed: 21368860doi: 10.1038/cddis.2010.67google scholar: lookup
  40. Udelnow A, Kreyes A, Ellinger S, Landfester K, Walther P, Klapperstueck T, Wohlrab J, Henne-Bruns D, Knippschild U, Würl P. Omeprazole inhibits proliferation and modulates autophagy in pancreatic cancer cells.. PLoS One 2011;6(5):e20143.
  41. Wojtkowiak JW, Rothberg JM, Kumar V, Schramm KJ, Haller E, Proemsey JB, Lloyd MC, Sloane BF, Gillies RJ. Chronic autophagy is a cellular adaptation to tumor acidic pH microenvironments.. Cancer Res 2012 Aug 15;72(16):3938-47.
  42. Roepe PD. pH and multidrug resistance.. Novartis Found Symp 2001;240:232-47; discussion 247-50, 265-8.
    doi: 10.1002/0470868716.ch16pubmed: 11727933google scholar: lookup
  43. Robey IF, Baggett BK, Kirkpatrick ND, Roe DJ, Dosescu J, Sloane BF, Hashim AI, Morse DL, Raghunand N, Gatenby RA, Gillies RJ. Bicarbonate increases tumor pH and inhibits spontaneous metastases.. Cancer Res 2009 Mar 15;69(6):2260-8.
  44. Spugnini EP, Baldi A, Buglioni S, Carocci F, de Bazzichini GM, Betti G, Pantaleo I, Menicagli F, Citro G, Fais S. Lansoprazole as a rescue agent in chemoresistant tumors: a phase I/II study in companion animals with spontaneously occurring tumors.. J Transl Med 2011 Dec 28;9:221.
    pmc: PMC3264547pubmed: 22204495doi: 10.1186/1479-5876-9-221google scholar: lookup
  45. Spugnini EP, Buglioni S, Carocci F, Francesco M, Vincenzi B, Fanciulli M, Fais S. High dose lansoprazole combined with metronomic chemotherapy: a phase I/II study in companion animals with spontaneously occurring tumors.. J Transl Med 2014 Aug 21;12:225.
    pmc: PMC4145230pubmed: 25143012doi: 10.1186/s12967-014-0225-ygoogle scholar: lookup
  46. . Veterinary cooperative oncology group - common terminology criteria for adverse events (VCOG-CTCAE) following chemotherapy or biological antineoplastic therapy in dogs and cats v1.1.. Vet Comp Oncol 2016 Dec;14(4):417-446.
    pubmed: 28530307doi: 10.1111/vco.283google scholar: lookup
  47. Spugnini EP, Citro G, Fais S. Proton pump inhibitors as anti vacuolar-ATPases drugs: a novel anticancer strategy.. J Exp Clin Cancer Res 2010 May 8;29(1):44.
    doi: 10.1186/1756-9966-29-44pmc: PMC2876100pubmed: 20459683google scholar: lookup
  48. Wen-Li Z, Jian W, Yan-Fang T, Xing F, Yan-Hong L, Xue-Ming Z, Min Z, Jian N, Jian P. Inhibition of the ecto-beta subunit of F1F0-ATPase inhibits proliferation and induces apoptosis in acute myeloid leukemia cell lines.. J Exp Clin Cancer Res 2012 Nov 9;31(1):92.
    pmc: PMC3503881pubmed: 23140181doi: 10.1186/1756-9966-31-92google scholar: lookup
  49. Lindner K, Borchardt C, Schöpp M, Bürgers A, Stock C, Hussey DJ, Haier J, Hummel R. Proton pump inhibitors (PPIs) impact on tumour cell survival, metastatic potential and chemotherapy resistance, and affect expression of resistance-relevant miRNAs in esophageal cancer.. J Exp Clin Cancer Res 2014 Sep 1;33(1):73.
    pmc: PMC4431491pubmed: 25175076doi: 10.1186/s13046-014-0073-xgoogle scholar: lookup
  50. Hornick JR, Vangveravong S, Spitzer D, Abate C, Berardi F, Goedegebuure P, Mach RH, Hawkins WG. Lysosomal membrane permeabilization is an early event in Sigma-2 receptor ligand mediated cell death in pancreatic cancer.. J Exp Clin Cancer Res 2012 May 2;31(1):41.
    pmc: PMC3414770pubmed: 22551149doi: 10.1186/1756-9966-31-41google scholar: lookup
  51. Malm SW, Hanke NT, Gill A, Carbajal L, Baker AF. The anti-tumor efficacy of 2-deoxyglucose and D-allose are enhanced with p38 inhibition in pancreatic and ovarian cell lines.. J Exp Clin Cancer Res 2015 Apr 1;34(1):31.
    doi: 10.1186/s13046-015-0147-4pmc: PMC4391305pubmed: 25888489google scholar: lookup
  52. Hu T, He N, Yang Y, Yin C, Sang N, Yang Q. DEC2 expression is positively correlated with HIF-1 activation and the invasiveness of human osteosarcomas.. J Exp Clin Cancer Res 2015 Feb 28;34(1):22.
    doi: 10.1186/s13046-015-0135-8pmc: PMC4379712pubmed: 25884381google scholar: lookup
  53. Shen H, Decollogne S, Dilda PJ, Hau E, Chung SA, Luk PP, Hogg PJ, McDonald KL. Dual-targeting of aberrant glucose metabolism in glioblastoma.. J Exp Clin Cancer Res 2015 Feb 5;34(1):14.
    pmc: PMC4324653pubmed: 25652202doi: 10.1186/s13046-015-0130-0google scholar: lookup
  54. Qin Q, Furong W, Baosheng L. Multiple functions of hypoxia-regulated miR-210 in cancer.. J Exp Clin Cancer Res 2014 Jun 9;33(1):50.
    doi: 10.1186/1756-9966-33-50pmc: PMC4060094pubmed: 24909053google scholar: lookup

Citations

This article has been cited 17 times.
  1. Toledo GF, Nagamine MK, Nowosh V, Machado FT, Massoco CO, Souza-Pinto NC, Dagli MLZ. Antineoplastic effects of sodium dichloroacetate and omeprazole, alone or in combination, on canine oral mucosal melanoma cells. Front Vet Sci 2023;10:1186650.
    doi: 10.3389/fvets.2023.1186650pubmed: 37520008google scholar: lookup
  2. Pillai K, Ke K, Mekkawy A, Akhter J, Morris DL. Enhancement of treatment efficacy of hepatic tumours using Trans-arterial-chemoembolization. Am J Cancer Res 2023;13(5):1623-1639.
    pubmed: 37293148
  3. Bhattacharya S, Khanam J, Sarkar P, Pal TK. A chemotherapeutic approach targeting the acidic tumor microenvironment: combination of a proton pump inhibitor and paclitaxel for statistically optimized nanotherapeutics. RSC Adv 2018 Dec 19;9(1):240-254.
    doi: 10.1039/c8ra08924hpubmed: 35521568google scholar: lookup
  4. Huntington KE, Louie A, Zhou L, Seyhan AA, Maxwell AW, El-Deiry WS. Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles. Am J Cancer Res 2022;12(1):138-151.
    pubmed: 35141009
  5. Halcrow PW, Geiger JD, Chen X. Overcoming Chemoresistance: Altering pH of Cellular Compartments by Chloroquine and Hydroxychloroquine. Front Cell Dev Biol 2021;9:627639.
    doi: 10.3389/fcell.2021.627639pubmed: 33634129google scholar: lookup
  6. Koltai T. Targeting the pH Paradigm at the Bedside: A Practical Approach. Int J Mol Sci 2020 Dec 3;21(23).
    doi: 10.3390/ijms21239221pubmed: 33287221google scholar: lookup
  7. Fais S, Marunaka Y. The Acidic Microenvironment: Is It a Phenotype of All Cancers? A Focus on Multiple Myeloma and Some Analogies with Diabetes Mellitus. Cancers (Basel) 2020 Nov 2;12(11).
    doi: 10.3390/cancers12113226pubmed: 33147695google scholar: lookup
  8. Koltai T. The Ph paradigm in cancer. Eur J Clin Nutr 2020 Aug;74(Suppl 1):14-19.
    doi: 10.1038/s41430-020-0684-6pubmed: 32873952google scholar: lookup
  9. Harguindey S, Alfarouk K, Orozco JP, Hardonniere K, Stanciu D, Fais S, Devesa J. A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics. Int J Mol Sci 2020 Feb 7;21(3).
    doi: 10.3390/ijms21031110pubmed: 32046158google scholar: lookup
  10. Pillai SR, Damaghi M, Marunaka Y, Spugnini EP, Fais S, Gillies RJ. Causes, consequences, and therapy of tumors acidosis. Cancer Metastasis Rev 2019 Jun;38(1-2):205-222.
    doi: 10.1007/s10555-019-09792-7pubmed: 30911978google scholar: lookup
  11. Alfarouk KO, Bashir AHH, Aljarbou AN, Ramadan AM, Muddathir AK, AlHoufie STS, Hifny A, Elhassan GO, Ibrahim ME, Alqahtani SS, AlSharari SD, Supuran CT, Rauch C, Cardone RA, Reshkin SJ, Fais S, Harguindey S. The Possible Role of Helicobacter pylori in Gastric Cancer and Its Management. Front Oncol 2019;9:75.
    doi: 10.3389/fonc.2019.00075pubmed: 30854333google scholar: lookup
  12. Poon AC, Inkol JM, Luu AK, Mutsaers AJ. Effects of the potassium-sparing diuretic amiloride on chemotherapy response in canine osteosarcoma cells. J Vet Intern Med 2019 Mar;33(2):800-811.
    doi: 10.1111/jvim.15382pubmed: 30556178google scholar: lookup
  13. Patil R, Kulshrestha A, Tikoo A, Fleetwood S, Katara G, Kolli B, Seibel W, Gilman-Sachs A, Patil SA, Beaman KD. Identification of Novel Bisbenzimidazole Derivatives as Anticancer Vacuolar (H⁺)-ATPase Inhibitors. Molecules 2017 Sep 16;22(9).
    doi: 10.3390/molecules22091559pubmed: 28926955google scholar: lookup
  14. Koltai T. Cancer: fundamentals behind pH targeting and the double-edged approach. Onco Targets Ther 2016;9:6343-6360.
    doi: 10.2147/OTT.S115438pubmed: 27799782google scholar: lookup
  15. Azzarito T, Lugini L, Spugnini EP, Canese R, Gugliotta A, Fidanza S, Fais S. Effect of Modified Alkaline Supplementation on Syngenic Melanoma Growth in CB57/BL Mice. PLoS One 2016;11(7):e0159763.
    doi: 10.1371/journal.pone.0159763pubmed: 27447181google scholar: lookup
  16. Cerioli N, Bououdina W, Mereu A, Natsaridis E, Salsetta J, Cova A, Lupoli G, D'Angelo E, Rivoltini L, Figdor CG, Huber V, Tagit O. Reprogramming the melanoma and immunosuppressive myeloid cells with esomeprazole-loaded PLGA nanoparticles. iScience 2025 Jan 17;28(1):111559.
    doi: 10.1016/j.isci.2024.111559pubmed: 39839438google scholar: lookup
  17. Aventaggiato M, Arcangeli T, Vernucci E, Barreca F, Sansone L, Pellegrini L, Pontemezzo E, Valente S, Fioravanti R, Russo MA, Mai A, Tafani M. Pharmacological Activation of SIRT3 Modulates the Response of Cancer Cells to Acidic pH. Pharmaceuticals (Basel) 2024 Jun 20;17(6).
    doi: 10.3390/ph17060810pubmed: 38931477google scholar: lookup