A Preclinical Orthotopic Model for Glioblastoma Multiforme that Represents Key Pathways Aberrant in Human Brain Cancer

Current therapies for glioblastoma multiforme (GBM), the highest grade malignant brain tumor, are mostly ineffective, and better preclinical model systems are needed to increase the successful translation of drug discovery efforts into the clinic. Scientists at the National Cancer Institute (NCI) have developed and characterized an orthotopic genetically engineered mouse (GEM)-derived model of GBM that closely recapitulates various human GBM subtypes and is useful for preclinical evaluation of candidate therapeutics. The GEM-derived GBM model harbors perturbations in the receptor tyrosine kinase (RTK), phosphoinositide 3-kinase (PI3K) and retinoblastoma (RB) tumor suppressor networks and develops spontaneous p53 aberrations upon induction of the constitutively active mutant KRASG12D and deletion of phosphatase and tensin homolog (PTEN) alleles; the orthotopically implanted mice are referred to as ‘TRP’ mice. The TRP mice develop high grade GBM that are histologically similar to human GBM within weeks allowing the creation of large preclinical cohorts that are tractable for therapeutic evaluation.  IC: NCINIH Ref. No.: E-246-2014Advantages: Rapid preclinical evaluation of therapeutics. Primary cells from the GEM-GBM injected orthotopically into immune competent syngeneic mice brains induce grade IV tumors within 2 to 3 weeks.The GEM-GBM model represents a range of GBM cell types, recapitulating the heterogeneous cell population found in human GBM.  GBM tu...
Source: NIH OTT Licensing Opportunities - Category: Research Authors: Source Type: research