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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

Loco-regional chemotherapy with patient alkalization in a 10 year old Arab mare. a Patient at presentation. b Ultrasound-guided intralesional chemotherapy with alkalization. c Tumor appearance after the 4th session
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Fig5: Loco-regional chemotherapy with patient alkalization in a 10 year old Arab mare. a Patient at presentation. b Ultrasound-guided intralesional chemotherapy with alkalization. c Tumor appearance after the 4th session

Mentions: A 10 year old Arabian mare was referred for multiple muco-cutaneous melanoma and for failure at conceiving. At presentation the horse was bright alert and responsive (Fig. 5a) and presented several melanomas ranging in size from 2 to 8 cm. Ultrasonographic examination was performed showing multiple lymph-nodal metastasis within the abdomen, some of them compressing the uterus and adnexa. Systemic chemotherapy treatment with platinum compounds was deemed unrealistic due to the widespread disease and related expenses with this therapy. At this point, intralesional chemotherapy with CDDP was offered as a palliation. The first course did not result in any measurable response and patient alkalization was then suggested. Considering the amount of PPI or H2 blockers needed to achieve this goal, a different approach was proposed: intralesional administration of bicarbonate combined with diet supplementation with the same substance since it is palatable to the horses. In this patient were performed 4 sessions of intralesional 8.4 % (w/v) bicarbonate solution followed by intralesional CDDP 0,5 % (w/v) solution under ultrasonographic guidance (Fig. 5b and c). This therapy yielded a 50 % lymph nodes tumour reduction after 3 sessions. The treatment was discontinued after the 4th session due to financial concerns. The horse has been kept on bicarbonate supplementation as maintenance and is actually experiencing a robust partial remission lasting in excess of two years. Throughout this period the mare has been showing a good quality of life. Side effects secondary to the therapy have not been reported. Alkalization obtained through diet supplementation or through the administration of pump inhibitors can be a valuable strategy to improve the efficacy of standard as well as non-conventional chemotherapy in veterinary oncology.Fig. 5


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)

Loco-regional chemotherapy with patient alkalization in a 10 year old Arab mare. a Patient at presentation. b Ultrasound-guided intralesional chemotherapy with alkalization. c Tumor appearance after the 4th session
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig5: Loco-regional chemotherapy with patient alkalization in a 10 year old Arab mare. a Patient at presentation. b Ultrasound-guided intralesional chemotherapy with alkalization. c Tumor appearance after the 4th session
Mentions: A 10 year old Arabian mare was referred for multiple muco-cutaneous melanoma and for failure at conceiving. At presentation the horse was bright alert and responsive (Fig. 5a) and presented several melanomas ranging in size from 2 to 8 cm. Ultrasonographic examination was performed showing multiple lymph-nodal metastasis within the abdomen, some of them compressing the uterus and adnexa. Systemic chemotherapy treatment with platinum compounds was deemed unrealistic due to the widespread disease and related expenses with this therapy. At this point, intralesional chemotherapy with CDDP was offered as a palliation. The first course did not result in any measurable response and patient alkalization was then suggested. Considering the amount of PPI or H2 blockers needed to achieve this goal, a different approach was proposed: intralesional administration of bicarbonate combined with diet supplementation with the same substance since it is palatable to the horses. In this patient were performed 4 sessions of intralesional 8.4 % (w/v) bicarbonate solution followed by intralesional CDDP 0,5 % (w/v) solution under ultrasonographic guidance (Fig. 5b and c). This therapy yielded a 50 % lymph nodes tumour reduction after 3 sessions. The treatment was discontinued after the 4th session due to financial concerns. The horse has been kept on bicarbonate supplementation as maintenance and is actually experiencing a robust partial remission lasting in excess of two years. Throughout this period the mare has been showing a good quality of life. Side effects secondary to the therapy have not been reported. Alkalization obtained through diet supplementation or through the administration of pump inhibitors can be a valuable strategy to improve the efficacy of standard as well as non-conventional chemotherapy in veterinary oncology.Fig. 5

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