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

Walsh M, Fais S, Spugnini EP, Harguindey S, Abu Izneid T, Scacco L, Williams P, Allegrucci C, Rauch C, Omran Z - J. Exp. Clin. Cancer Res. (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Veterinary Medicine and Science, University of Nottingham, College Road, Sutton Bonington, LE12 5RD, UK. Megan.walsh@nottingham.ac.uk.

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.

No MeSH data available.


Related in: MedlinePlus

pH regulation in cancer cells. A number of proteins and chemical reactions regulates pH in cells. The present review focuses on NHE1 and V-ATPase. 1: CAs, 2: ATP-Synthase, 3: NHE1, 4: MCTs, 5: V-H+-ATPase, 6: Cl−/HCO3−. pHi = Intracellular pH. pHe = Extracellular pH [28]
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Fig1: pH regulation in cancer cells. A number of proteins and chemical reactions regulates pH in cells. The present review focuses on NHE1 and V-ATPase. 1: CAs, 2: ATP-Synthase, 3: NHE1, 4: MCTs, 5: V-H+-ATPase, 6: Cl−/HCO3−. pHi = Intracellular pH. pHe = Extracellular pH [28]

Mentions: One way cancer cells avoid the accumulation of intracellular acid is by the up-regulation of proton pumps (PP) and transporters (PTI) responsible for the removal of hydrogen ions from the intracellular compartments or cytosol to the extracellular microenvironment. Several biological mechanisms exist to export hydrogen ions out of the cells and to affect the extracellular pH including the carbonic anhydrase (CA) enzymes (and in particular CA IX) [9], the monocarboxylic transporters (MCT), the Vacuolar-H + −ATPase (V-ATPase) and the Na+/H+ transporters (NHE) [1] (Fig. 1).Fig. 1


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

Walsh M, Fais S, Spugnini EP, Harguindey S, Abu Izneid T, Scacco L, Williams P, Allegrucci C, Rauch C, Omran Z - J. Exp. Clin. Cancer Res. (2015)

pH regulation in cancer cells. A number of proteins and chemical reactions regulates pH in cells. The present review focuses on NHE1 and V-ATPase. 1: CAs, 2: ATP-Synthase, 3: NHE1, 4: MCTs, 5: V-H+-ATPase, 6: Cl−/HCO3−. pHi = Intracellular pH. pHe = Extracellular pH [28]
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4559889&req=5

Fig1: pH regulation in cancer cells. A number of proteins and chemical reactions regulates pH in cells. The present review focuses on NHE1 and V-ATPase. 1: CAs, 2: ATP-Synthase, 3: NHE1, 4: MCTs, 5: V-H+-ATPase, 6: Cl−/HCO3−. pHi = Intracellular pH. pHe = Extracellular pH [28]
Mentions: One way cancer cells avoid the accumulation of intracellular acid is by the up-regulation of proton pumps (PP) and transporters (PTI) responsible for the removal of hydrogen ions from the intracellular compartments or cytosol to the extracellular microenvironment. Several biological mechanisms exist to export hydrogen ions out of the cells and to affect the extracellular pH including the carbonic anhydrase (CA) enzymes (and in particular CA IX) [9], the monocarboxylic transporters (MCT), the Vacuolar-H + −ATPase (V-ATPase) and the Na+/H+ transporters (NHE) [1] (Fig. 1).Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: School of Veterinary Medicine and Science, University of Nottingham, College Road, Sutton Bonington, LE12 5RD, UK. Megan.walsh@nottingham.ac.uk.

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.

No MeSH data available.


Related in: MedlinePlus