Monday 9 January 2012

Q&A With Dr Stefano Fais - PPI and Cancer

In a previous article I highlighted some recent results of the work of Dr Stefano Fais and his colleagues in using the over the counter gastric acid treatment lansoprazole to stop tumours becoming resistant to chemotherapy. Lansoprazole is one of a family of drugs called proton pump inhibitors (PPI), that are targeted at highly acidic environments in the body - and tumours, as is well known, create very highly acidic microenvironments. As chemo-resistance is a major problem in oncology, leading to treatment failure in many patients, this is important work. Kindly Dr Fais has agreed to answer a few questions for

PP: Why is it important to focus on the tumour microenvironment?
SF: Because malignant cells are progressively selected within the tumor mass for their ability to survive in a very hostile microenvironment, an environment that is generated by their own metabolism. In fact, in the same microenvironment either normal cells or more differentiated cells usually die. Tumor cells survive thanks to some mechanisms them  to quickly eliminate toxins, which would otherwise be able to kill them if they were free to accumulate.

PP: What has been the pre-clinical experience with PPI treatment and cancer in people?
SF: Proton pump inhibitors actually block a mechanism that on one hand induces acidification of extracellular environment, in turn impairing both the body’s reaction to the tumor and also highly reducing the efficacy of drugs that are neutralized by the acidic microenvironment. In fact, pre-clinical data have shown that PPI can increase the efficacy of current anti-tumor therapies and induce a real anti-tumor effect by depriving tumor cells of a key survival mechanism.
PP: What are the current and future plans for clinical trials?
SF: The current clinical trials are on the chemosensitizing effect of PPI in patients affected by different malignant tumors, such as melanoma, osteosarcoma, breast cancer and gastric cancer. The results are really encouraging but we have a lot of work to do to set up the treatment schedule and the dosage, probably cancer by cancer and patient by patient.

PP: How much interest is there from mainstream oncologists in the work on PPI and other agents that target tumour acidity?
SF: Oncologists are too often skeptical of this approach. On the one hand they are resistant in believing that such an unaggressive treatment may be effective in patients where normally even the poisons do not work. Then they are basically chemotherapists, without any belief in other approaches. Then they are more prone to believe in new treatment as proposed by the Big pharma with a high level of investment and money for clinical trials. However, sometimes you can find more open mind oncologists.

PP: Has there been any work on combining sodium bicarbonate and PPI?
SF: Not yet, but it has to be done.

PP: Does high-dose PPI treatment interact with other 'off-label' drugs used for cancer - metformin, celecoxib, beta blockers etc?
SF: At the moment we don’t know and it is hard to obtain substantial data in short times

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