Combinatorial Therapies for Neurofibroma and MPNST Treatment and Prevention
Technical Report,01 Aug 2016,31 Jul 2017
Medical University of South Carolina Charleston United States
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We hypothesize that tamoxifen, trifluoperazine or combined tamoxifen-trifluoperazine therapy will effectively treat established neurofibromas and MPNSTs and prolong survival. We also hypothesize that prophylactic treatment with these drugs will prevent neurofibroma and MPNST pathogenesis. To test these hypotheses, we will 1 determine whether tamoxifen, trifluoperazine or tamoxifen-trifluoperazine therapy effectively inhibits tumor cell proliferation and survival in established neurofibromas and MPNSTs and prolongs the survival of mice with these tumors and 2 determine whether prophylactic therapy with tamoxifen andor trifluoperazine will prevent the pathogenesis of neurofibromas and MPNSTs. These preclinical trials will be performed using robust mouse models of neurofibroma Krox20-CreNf1flox- mice and MPNST P0-GGFbeta3Trp53- mice pathogenesis. In Aim 1, mice with established neurofibromas and MPNSTs will be challenged with vehicle, tamoxifen, trifluoperazine or combined tamoxifen-trifluoperazine therapy and we will establish which of these treatments maximally inhibits tumor cell proliferation and survival and improves long term survival. In Aim 2, we will begin treatment of Krox20-CreNf1flox- and P0-GGFbeta3Trp53- mice with vehicle, tamoxifen, trifluoperazine or tamoxifen-trifluoperazine prior to the development of tumors and continue this treatment to 15 months of age. We will then determine if these prophylactic therapies prevent neurofibroma and MPNST pathogenesis or reduce the number and size of tumors in our mice.
- Medicine and Medical Research