New Therapeutic Paradigms
Metabolic Dysregulation in Tumors
Metabolic dysregulation in tumors is a topic of intense interest in the study of cancer. We are investigating the therapeutic value of
a using a high-fat, low-carbohydrate ketogenic diet to alter the cellular metabolism of tumors in combination with traditional radiation and chemotherapy. This diet is a highly regimented, established nonpharmacologic treatment for refractory epilepsy. We have found that it slows the growth of brain tumor cells in laboratory experiments and enhances survival in a murine model of malignant brain tumors. When combined with radiation or Temodar®, it significantly increased survival. Molecular analysis of the mechanism of action has demonstrated multiple effects on tumors, including:
- A reduction in the expression of genes involved in growth factor pathways known to be involved in tumor growth
- An overall change in gene expression to a state similar to that seen in normal brain
- Reductions in angiogenesis, peritumoral edema, inflammation, and hypoxia
- A reduction in the expression of a variety of transcriptional activators
- Alterations in the epigenetic landscape of tumors in response to ketones
Our recent collaboration with Drs. Danielle Lussier and Joseph Blattman at Arizona State University has shown that the ketogenic diet also enhances the antitumor immune effect. Our current studies are aimed at identifying the molecular and epigenetic basis for these pluripotent antitumor effects.
Biomarkers for Brain Tumors
In collaboration with investigators at the Biodesign Institute at Arizona State University, we have developed immunosignature (IS) profiles that can be used to diagnose brain tumors and predict their course in vivo. Based on this research, an NIH SBIR grant has been awarded to HealthTell (a spinoff company originating from the Biodesign Institute) entitled Immune-Based Brain Cancer Diagnostics for Rapid, Accurate Disease Classifications.
This technology, which is relatively inexpensive and uses only a small drop of the patient’s blood, is being leveraged to create a test that not only aids in the diagnosis of brain tumors, but also distinguishes between tumor recurrence and treatment effect when changes occur on magnetic resonance imaging (MRI). We also think that it has the potential to detect tumor recurrence before changes manifest on MRI.
Intraoperative and Noninvasive Imaging
There is a great deal of interest in the use of intraoperative noninvasive imaging and biomarkers for patient care. We are involved in collaborative efforts with neurosurgery research at Barrow to develop new intraoperative confocal microscopes and technology.
Our project with Carl Zeiss, Inc. has led to a number of publications and ongoing testing of additional prototypes. A recent collaboration with Dr. Peter Nakaji has produced an NIH grant entitled The use of Switchable Molecular Nanoprobes for Fast and Specific Intraoperative Diagnosis of Brain Tumors.