Tumor metabolism (2006-present)
We have initiated several studies in tumor metabolism. We are testing whether reversing the Warburg effect will affect tumor cells preferentially. This appears to be the case. We are using both RNAi and pharmacologic inhibitors to approach this question with a focus on several genes involved with altering the fate of pyruvate. Other studies are focused on inhibitors of fatty acid and cholesterol synthesis. Yet others focus on a gene in the pentose phosphate pathway and on inhibition of various mitochondrial targets and the ways in which mitochondria signal to canonical oncogenic pathways in the cytosol. We are also examining strategies to decrease intracellular pH by inhibiting export of protons. We are collaborating with MRI experts in our radiology department to non-invasively visualize metabolic fluxes using hyperpolarized carbon substrates.
Tumor immunotherapy (2007-present)
We have initiated studies in tumor immunology with the aim of breaking the tolerant state engendered by tumors. The focus is on defining how tumors generate a population of suppressor cells known as myeloid derived suppressor cells. We are characterizing these cells molecularly by defining novel surface markers that and assaying for drug combinations that in vivo will simultaneously inhibit both these cells and T regulatory cells. Initial studies are in melanoma and pancreatic, lung and breast cancer models in both genetically engineered and transplant systems.
“Outside of the box” cancer therapies (2005-present)
We are cataloguing case reports of cancer remissions on protocols or drug regimens that are not considered standard of care. We are also scouring published preclinical data in cancer models using FDA approved non-cancer drugs (see below) that might be interesting to take to the clinic. We are conducting additional pre-clinical studies especially with such drugs in combinations and are committed to taking them to the clinic for patients with advanced cancer who have exhausted conventional options. We are also investigating drugs/therapies that are off patent or were never patented, hence making them unattractive to the pharmaceutical sector. We are co-founders of a not-for-profit organization (GlobalCures) that aims to develop such therapies for human studies. We are especially interested in promoting drug combinations which have clear-cut mechanisms of action.