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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

Metronomic chemotherapy with patient alkalization in a 15 year old mixed breed with lung carcinoma. a Tumor appearance at presentation (CT scan imaging). b Tumor appearance after 14 months of therapy (thoracic radiograph imaging)
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Fig4: Metronomic chemotherapy with patient alkalization in a 15 year old mixed breed with lung carcinoma. a Tumor appearance at presentation (CT scan imaging). b Tumor appearance after 14 months of therapy (thoracic radiograph imaging)

Mentions: A 15 year old male mixed breed dog was referred for oncology consult due to persistent coughing that lasted in excess of one month, unresponsive to symptomatic therapy. The dog was quiet, alert and responsive at physical exam, cardiac function upon auscultation was within normal limits, in the right thoracic side respiratory sounds were muffled and there was a 5 cm area were the sounds could not be appreciated at all. Cough was easily induced upon tracheal stimulation. Haematological analysis and biochemical profile showed a mild anaemia (5.2 x 106/μL RBC with a lower limit of 5.5). Chest radiographs evidenced a mass in the left lung. At this point a CT scan study was deemed necessary to perform a biopsy under guidance (Fig. 4a). The report came back with a diagnosis of bronchogenic carcinoma. The treatment options were discussed with the owner and included lobectomy combined with systemic chemotherapy, systemic chemotherapy alone or metronomic chemotherapy with alkalinisation of the patients. The owner, due to emotional and financial issues chose the third option. The patient was treated with a combination of daily cyclophosphamide, piroxicam and lansoprazole as previously described [45] combined with a water alkalizer. The therapy was well tolerated and the cough subsided, while the patient showed an increased activity level as well as improved quality of life. Side effects were confined to 3 episodes of grade 2 gastrointestinal toxicoses [46] and a mild worsening of the anemia after 8 months of therapy (RBC 4.8 × 106/μL). After 14 months the patient is still in a condition of stable disease and is monitored with chest radiographs every two months (Fig. 4b).Fig. 4


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)

Metronomic chemotherapy with patient alkalization in a 15 year old mixed breed with lung carcinoma. a Tumor appearance at presentation (CT scan imaging). b Tumor appearance after 14 months of therapy (thoracic radiograph imaging)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig4: Metronomic chemotherapy with patient alkalization in a 15 year old mixed breed with lung carcinoma. a Tumor appearance at presentation (CT scan imaging). b Tumor appearance after 14 months of therapy (thoracic radiograph imaging)
Mentions: A 15 year old male mixed breed dog was referred for oncology consult due to persistent coughing that lasted in excess of one month, unresponsive to symptomatic therapy. The dog was quiet, alert and responsive at physical exam, cardiac function upon auscultation was within normal limits, in the right thoracic side respiratory sounds were muffled and there was a 5 cm area were the sounds could not be appreciated at all. Cough was easily induced upon tracheal stimulation. Haematological analysis and biochemical profile showed a mild anaemia (5.2 x 106/μL RBC with a lower limit of 5.5). Chest radiographs evidenced a mass in the left lung. At this point a CT scan study was deemed necessary to perform a biopsy under guidance (Fig. 4a). The report came back with a diagnosis of bronchogenic carcinoma. The treatment options were discussed with the owner and included lobectomy combined with systemic chemotherapy, systemic chemotherapy alone or metronomic chemotherapy with alkalinisation of the patients. The owner, due to emotional and financial issues chose the third option. The patient was treated with a combination of daily cyclophosphamide, piroxicam and lansoprazole as previously described [45] combined with a water alkalizer. The therapy was well tolerated and the cough subsided, while the patient showed an increased activity level as well as improved quality of life. Side effects were confined to 3 episodes of grade 2 gastrointestinal toxicoses [46] and a mild worsening of the anemia after 8 months of therapy (RBC 4.8 × 106/μL). After 14 months the patient is still in a condition of stable disease and is monitored with chest radiographs every two months (Fig. 4b).Fig. 4

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