University of Miami
Miami, United States
Antonio Iavarone, M.D.. Professor of Neurological Surgery and Biochemistry University of Miami Miller School of Medicine
The overarching theme of my research program is to unravel the irreplaceable and homogeneous biologic and genetic alterations driving subgroups of malignant brain tumors and exploit this information for rational therapeutic stratification. We discovered the first example of oncogenic and tumor addicting gene fusions in malignant glioma (FGFR3-TACC3) and reported that FGFR3-TACC3 fusions trigger tumorigenesis through activation of oxidative phosphorylation. From our work, we designed two international multi-Institution trials for precision targeting of GBM patients harboring FGFR3TACC3. This fusion, which is druggable, is commonly present in other tumors, and is targeted by clinical trials I am co-leading, led to the recent FDA approval of the clinical-grade screening assay developed in my lab for unbiased identification of FGFR3-TACC3 variants as companion diagnostics. My program recently reached the stage of consortium activities that I have been chairing for the deconvolution of the molecular landscape of sporadic glioma (ATLAS-TCGA) and genetically predisposed brain tumors (NF1 synodos network) with consequent introduction of accurate therapeutic predictions in the clinical setting. We recently developed an unbiased, pathway-based computational framework for the extraction of the master biological traits of single cancer cells that is the basis of this grant proposal. This work led to the formulation of a new classification of malignant glioma that for the first time introduced the opportunity of clinical stratification and targeted vulnerability in GBM. It has recently been applied to CPTAC datasets to provide the basis for this application, particularly in the context of the explosive new paradigm of “cancer neuroscience” to disentanbgle many mysterious aspects of brain tumor biology.
