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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

Dose response toxicity curve of canine osteosarcoma D17 sarcospheres treated with omeprazole and amiloride, as assessed by flow cytometry (a). Effect of pre-treating sarcospheres with omeprazole and amiloride prior to treatment with doxorubicin and cisplatin versus chemotherapeutic drug alone (b)
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Fig3: Dose response toxicity curve of canine osteosarcoma D17 sarcospheres treated with omeprazole and amiloride, as assessed by flow cytometry (a). Effect of pre-treating sarcospheres with omeprazole and amiloride prior to treatment with doxorubicin and cisplatin versus chemotherapeutic drug alone (b)

Mentions: This is supported by evidence collected during in vitro preliminary studies performed by the authors which showed cellular death was increased in a dose dependent manner using the PPI omeprazole and the NHE blocker amiloride in canine osteosarcoma cells (Fig. 3a). The study performed in chemoresistant sarcospheres derived from canine osteosarcoma cells shows a dose dependent toxic response to the PPI and NHE blocker. In addition , the results show increased cell death when the sarcospheres were pre-treated with PPI/NHE blocker compared to using doxorubicin or cisplatin alone (Fig. 3b).Fig. 3


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)

Dose response toxicity curve of canine osteosarcoma D17 sarcospheres treated with omeprazole and amiloride, as assessed by flow cytometry (a). Effect of pre-treating sarcospheres with omeprazole and amiloride prior to treatment with doxorubicin and cisplatin versus chemotherapeutic drug alone (b)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig3: Dose response toxicity curve of canine osteosarcoma D17 sarcospheres treated with omeprazole and amiloride, as assessed by flow cytometry (a). Effect of pre-treating sarcospheres with omeprazole and amiloride prior to treatment with doxorubicin and cisplatin versus chemotherapeutic drug alone (b)
Mentions: This is supported by evidence collected during in vitro preliminary studies performed by the authors which showed cellular death was increased in a dose dependent manner using the PPI omeprazole and the NHE blocker amiloride in canine osteosarcoma cells (Fig. 3a). The study performed in chemoresistant sarcospheres derived from canine osteosarcoma cells shows a dose dependent toxic response to the PPI and NHE blocker. In addition , the results show increased cell death when the sarcospheres were pre-treated with PPI/NHE blocker compared to using doxorubicin or cisplatin alone (Fig. 3b).Fig. 3

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