One of the most common genetic aberration in glioblastoma (GBM) is the activation of receptor tyrosine kinases (RTKs). Amongst the 58 known RTKs, 8 receptors have been reported to be aberrantly expressed in GBMs with mutations of the epidermal growth factor receptor (EGFR) being by far the most common occurrence. This high frequency of amplifications and/or mutations of RTKs in GBM are evocative of their role in key aspects of GBM biology which makes them therapeutically appealing.

My group utilizes strategies that are designed to counteract RTK-mediated oncogenic stimuli in animal models of GBM based on the RTKs ROS and EGFR. We are utilizing a systematic approach aimed at establishing a functional relationship between activation of RTKs and ensuing tumor phenotypes in an in vivo environment. Such endeavor would generate invaluable information on RTKs' roles in GBM behavior. The identification of signaling molecules necessary for critical aspects of GBM biology such as tumor initiation, establishment, and maintenance and, most importantly, resistance to treatment offers opportunities for pharmaceutical exploitation. Combining individualized, molecularly-tailored therapies with standard disease management treatments represents a promising strategy to disease containment and, hopefully, eradication.

In addition to therapeutically targeting the receptors themselves, many signaling members are quite amenable to the utilization of RNAi as therapeutics. My laboratory is developing siRNA vector systems that will allow for a systematic dissection of key components of a given pathway during tumor initiation and maintenance.

To learn more about the use of siRNA molecules as therapeutics in mouse models of brain cancers click here.

Preclinical testing of potential therapeutics is hampered by the inherent difficulties in studying intracranial tumor growth parameters. A major facet of our work entails the creation of new tools for monitoring tumor growth in a non-invasive fashion in live animals. Bio-imaging offers a methodology by which tumor response to various compounds can be tracked in a single animal over time. For basic testing of tumor response to therapy, bioluminescence (BLI) offers marked advantages over more conventional imaging technologies (MRIs or CT Scans).

Finally, my group has created and validated conditional bioluminescent luciferase reporter strains that will allow a temporal ascertainment of treatment efficacy in our GBM models. We will continue to develop non-invasive bioimaging tools for use in preclinical testing of therapeutics.