Efficacy of cabazitaxel in mouse models of pediatric brain tumors

作者：Emily J. Girard, Sally Ditzler, Donghoon Lee, Andrew Richards, Kevin Yagle, Joshua Park, Hedieh K. Eslamy, Dmitri Bobilev, Patricia Vrignaud, James M. Olson · 发表于：Neuro-Oncology · 年份：2014 · DOI：10.1093/neuonc/nou163 · 被引用次数：44 · 研究领域：Chromatin Remodeling and Cancer、Glioma Diagnosis and Treatment、Hedgehog Signaling Pathway Studies

BACKGROUND: There is an unmet need in the treatment of pediatric brain tumors for chemotherapy that is efficacious, avoids damage to the developing brain, and crosses the blood-brain barrier. These experiments evaluated the efficacy of cabazitaxel in mouse models of pediatric brain tumors. METHODS: The antitumor activity of cabazitaxel and docetaxel were compared in flank and orthotopic xenograft models of patient-derived atypical teratoid rhabdoid tumor (ATRT), medulloblastoma, and central nervous system primitive neuroectodermal tumor (CNS-PNET). Efficacy of cabazitaxel and docetaxel were also assessed in the Smo/Smo spontaneous mouse medulloblastoma tumor model. RESULTS: This study observed significant tumor growth inhibition in pediatric patient-derived flank xenograft tumor models of ATRT, medulloblastoma, and CNS-PNET after treatment with either cabazitaxel or docetaxel. Cabazitaxel, but not docetaxel, treatment resulted in sustained tumor growth inhibition in the ATRT and medulloblastoma flank xenograft models. Patient-derived orthotopic xenograft models of ATRT, medulloblastoma, and CNS-PNET showed significantly improved survival with treatment of cabazitaxel. CONCLUSION: These data support further testing of cabazitaxel as a therapy for treating human pediatric brain tumors.