The goal of this PS-OC is rapid translation of theoretical and experimental results into clinical applications. In fact, interest in perturbation of the physical microenvironment was first reported in 1798 by John Ewart, M.D. who successfully treated two breast cancer patients with carbonic acid.
Bicarbonate as a Therapeutic: In Projects 1& 2, when bicarbonate was administered to experimental animals, inhibition in growth of metastases was observed. In addition, tumor acid concentrations may play a key role in cancer-related pain, which has previously been attributed to local biomechanical disruption. Interestingly, there is recent evidence that pain fibers are acid-sensitive and that tumor-induced pain may be caused by regional acidosis. Finally, recent modeling results have suggested that disruption of the physical microenvironment in in-situ cancers either by intermittent, transient systemic acidosis (such as seen with exercise) or chronic administration of increased buffer will delay or even prevent transition to invasive cancer.
Two clinical trials are underway:
- The role of systemic administration of sodium bicarbonate in cancer-related pain.
- A phase 1/2 trial of sodium bicarbonate added to gemcitabine in patients with advanced pancreatic cancer.
An additional trial examining the role of sodium bicarbonate in delaying tumor recurrence in patients with pancreatic cancer following Whipple procedure is in preparation. For tumor prevention, we are using TRAMP mice which develop prostate cancer by age 20 weeks. In the treatment group we are adding sodium bicarbonate to their water to see if this delays onset of invasive cancer.
Predicting Patient-Specific Tumor Hypoxia and Associated Virtual FMISO-PET: Project 3 is developing and validating a set of mathematical modeling tools for predicting spatial maps of hypoxia (visualized through [18F]-fluoromisonidazole PET, FMISO) in individual glioma patients using only routinely available serial MRIs as inputs. This tool quantitatively connects patient-specific tumor growth and invasion kinetics with the physical microenvironment in vivo in individual patients.