Emily Girard1, Sally Ditzler1, Donghoon Lee1, Andrew Richards1, Kevin Yagle1, Joshua Park1, Hedieh Eslamy1, Dmitri Bobilev1, Patricia Vrignaud1, James Olson1. 1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington (E.G., S.D., A.R., J.O.); Department of Radiology, University of Washington, Seattle, Washington (D.L., K.Y., J.P., H.E.); Sanofi Oncology, Global Oncology Division, Cambridge, Massachusetts 02142 (D.B.); Oncology/Translational and Experimental Medicine, Sanofi Inc, Vitry sur Seine, France (P.V.).
Abstract
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.
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 mousemedulloblastoma 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 humanpediatric brain tumors.
Authors: Andrew J Bishop; Mark W McDonald; Andrew L Chang; Natia Esiashvili Journal: Int J Radiat Oncol Biol Phys Date: 2010-10-29 Impact factor: 7.038
Authors: Lisa Diller; Eric J Chow; James G Gurney; Melissa M Hudson; Nina S Kadin-Lottick; Toana I Kawashima; Wendy M Leisenring; Lillian R Meacham; Ann C Mertens; Daniel A Mulrooney; Kevin C Oeffinger; Roger J Packer; Leslie L Robison; Charles A Sklar Journal: J Clin Oncol Date: 2009-04-13 Impact factor: 44.544
Authors: Malcolm A Smith; Nita L Seibel; Sean F Altekruse; Lynn A G Ries; Danielle L Melbert; Maura O'Leary; Franklin O Smith; Gregory H Reaman Journal: J Clin Oncol Date: 2010-04-19 Impact factor: 44.544
Authors: Michael C Frühwald; Jaclyn A Biegel; Franck Bourdeaut; Charles W M Roberts; Susan N Chi Journal: Neuro Oncol Date: 2016-01-10 Impact factor: 12.300
Authors: John Glod; Gilbert J Rahme; Harpreet Kaur; Eric H Raabe; Eugene I Hwang; Mark A Israel Journal: J Pediatr Hematol Oncol Date: 2016-05 Impact factor: 1.289
Authors: Laura A Genovesi; Simon Puttick; Amanda Millar; Marija Kojic; Pengxiang Ji; Anne K Lagendijk; Caterina Brighi; Claudine S Bonder; Christelle Adolphe; Brandon J Wainwright Journal: Neuro Oncol Date: 2021-05-05 Impact factor: 12.300
Authors: Jasmin Bartl; Marco Zanini; Flavia Bernardi; Antoine Forget; Lena Blümel; Julie Talbot; Daniel Picard; Nan Qin; Gabriele Cancila; Qingsong Gao; Soumav Nath; Idriss Mahoungou Koumba; Marietta Wolter; François Kuonen; Maike Langini; Thomas Beez; Christopher Munoz; David Pauck; Viktoria Marquardt; Hua Yu; Judith Souphron; Mascha Korsch; Christina Mölders; Daniel Berger; Sarah Göbbels; Frauke-Dorothee Meyer; Björn Scheffler; Barak Rotblat; Sven Diederichs; Vijay Ramaswamy; Hiromishi Suzuki; Anthony Oro; Kai Stühler; Anja Stefanski; Ute Fischer; Gabriel Leprivier; Dieter Willbold; Gerhard Steger; Alexander Buell; Marcel Kool; Peter Lichter; Stefan M Pfister; Paul A Northcott; Michael D Taylor; Arndt Borkhardt; Guido Reifenberger; Olivier Ayrault; Marc Remke Journal: Nat Commun Date: 2022-07-13 Impact factor: 17.694
Authors: C Patrick Reynolds; Min H Kang; John M Maris; E Anders Kolb; Richard Gorlick; Jianrong Wu; Raushan T Kurmasheva; Peter J Houghton; Malcolm A Smith Journal: Pediatr Blood Cancer Date: 2015-07-07 Impact factor: 3.167
Authors: Yanxin Pei; Kun-Wei Liu; Jun Wang; Alexandra Garancher; Ran Tao; Lourdes A Esparza; Donna L Maier; Yoko T Udaka; Najiba Murad; Sorana Morrissy; Huriye Seker-Cin; Sebastian Brabetz; Lin Qi; Mari Kogiso; Simone Schubert; James M Olson; Yoon-Jae Cho; Xiao-Nan Li; John R Crawford; Michael L Levy; Marcel Kool; Stefan M Pfister; Michael D Taylor; Robert J Wechsler-Reya Journal: Cancer Cell Date: 2016-03-14 Impact factor: 31.743
Authors: Ran Tao; Najiba Murad; Zhenhua Xu; Peng Zhang; Konstantin Okonechnikov; Marcel Kool; Samuel Rivero-Hinojosa; Christopher Lazarski; Pan Zheng; Yang Liu; Charles G Eberhart; Brian R Rood; Roger Packer; Yanxin Pei Journal: Cancer Res Date: 2019-03-12 Impact factor: 13.312
Authors: Raelene Endersby; Jacqueline Whitehouse; Allison Pribnow; Mani Kuchibhotla; Hilary Hii; Brooke Carline; Suresh Gande; Jennifer Stripay; Mathew Ancliffe; Meegan Howlett; Tobias Schoep; Courtney George; Clara Andradas; Patrick Dyer; Marjolein Schluck; Brett Patterson; Silvia K Tacheva-Gigorova; Matthew N Cooper; Giles Robinson; Clinton Stewart; Stefan M Pfister; Marcel Kool; Till Milde; Amar Gajjar; Terrance Johns; Robert J Wechsler-Reya; Martine F Roussel; Nicholas G Gottardo Journal: Sci Transl Med Date: 2021-01-20 Impact factor: 19.319
Authors: Melissa J Davis; Brandon J Wainwright; Laura A Genovesi; Amanda Millar; Elissa Tolson; Matthew Singleton; Emily Hassall; Marija Kojic; Caterina Brighi; Emily Girard; Clara Andradas; Mani Kuchibhotla; Dharmesh D Bhuva; Raelene Endersby; Nicholas G Gottardo; Anne Bernard; Christelle Adolphe; James M Olson; Michael D Taylor Journal: Genome Med Date: 2021-06-21 Impact factor: 11.117