Created By Sara Gosline sgosline

summary: The objective of Project 1 is to extend these promising data to investigate the developmental, molecular, and pharmacokinetic effects of c-kit and MEK inhibition alone and in combination. Our investigative team will characterize the adaptive responses of PNs to these kinase inhibitors in GEM models and in parallel studies in patients. The aims of Project 1 are: Aim 1: Evaluate tumor and circulating markers before and after treatment with the MEK inhibitor selumetinib in pediatric and adult patients with NF1 associated plexiform neurofibromas. Aim 2: Evaluate the molecular adaptive responses, PK/PD and clinical response of plexiform neurofibromas in genetically engineered mice (GEM) with selumetinib alone, and in combination with imatinib mesylate. Aim 3: Utilize GEM models to identify the optimal therapeutic window(s) of c-kit (SCF) inhibition at distinct embryonic and adult stages of PN formation utilizing Nf1flox/- and Nf1flox/-;Scf flox/flox mice under the transcriptional control of a PLP tamoxifen + Cre transgene. The translational impact of this project involves: (1) defining therapeutic window(s) for c-kit inhibition at distinct embryonic and adult stages of PN formation; (2) investigating a rational approach to combinatorial therapy based on simultaneously interfering with paracrine growth signals emanating from the tumor microenvironment while also targeting aberrant Raf/MEK/ERK pathway activation in tumor cells; and (3) defining novel biomarkers by analyzing tumor specimens and blood obtained both prior to and after treatment.
tumorType: Plexiform Neurofibroma,MPNST
consortium: DHART SPORE
dataStatus: underEmbargo
projectName: DHART SPORE
diseaseFocus: Neurofibromatosis 1
institutions: Indiana University School of Medicine;Johns Hopkins Medical Institute;National Institute of Health;University of Texas, Southwestern
projectLeads: Wade Clapp;Jaishri Blakeley;Brigitte Widemann;Lu Le
fundingAgency: NIH-NCI
projectStatus: Active
summarySource: https://trp.cancer.gov/spores/abstracts/indiana_hyperactive.htm
projectFileviewId: syn11581437

DHART SPORE page is loading…