We have shown in multiple systems that oral buffers (e.g., bicarbonate, Tris, lysine, imidazoles) specifically increase tumor pH without affecting systemic pH balance, rarely affect primary tumor growth, but potently inhibit experimental or spontaneous metastases (1-6). These effects are also manifest in genetically engineered mouse cancer models (GEMMs). For example, in the TRAMP prostate model, the initiation of buffer therapy at 4 weeks of age prevents emergence of cancer (7), but if administered after 10 weeks (after tumors are extracapsular), it has no effect on the primary tumor, but completely inhibits metastases (8).
Similarly, in the KPC pancreatic cancer and HER2/neu breast cancer mouse models, buffer therapy, when given early, delays tumor onset (Ibrahim-Hashim et al., in prep).
The effect of NaHCO3 treatment on tumor pH using magnetic resonance imaging spectrometer (Robey et al)
To translate these provocative studies into the clinic we initiated phase I/II clinical trials of buffer monotherapy in pain management trials (NCT01350583/ 01846429) and pancreatic cancer patients (NCT01198821). However, these trials failed due to poor compliance, poor taste, and/or GI intolerability. Thus, we propose to develop pharmacological alternatives to achieve the same result (i.e., reducing tumor acidity).
Lung metastases of mice bearing GFP-expressing MDA-mb-231 breast cancer xenografts treated with bicarbonate (Robey et al.)
Arig Ibrahim-Hashim, MD