TY  - JOUR
AU  - Simovic, Milena
AU  - Bolkestein, Michiel
AU  - Moustafa, Mahmoud
AU  - Wong, John K L
AU  - Körber, Verena
AU  - Benedetto, Sarah
AU  - Khalid, Umar
AU  - Schreiber, Hannah Sophia
AU  - Jugold, Manfred
AU  - Korshunov, Andrey
AU  - Hübschmann, Daniel
AU  - Mack, Norman
AU  - Brons, Stephan
AU  - Wei, Pei-Chi
AU  - Breckwoldt, Michael O
AU  - Heiland, Sabine
AU  - Bendszus, Martin
AU  - Jürgen, Debus
AU  - Höfer, Thomas
AU  - Zapatka, Marc
AU  - Kool, Marcel
AU  - Pfister, Stefan M
AU  - Abdollahi, Amir
AU  - Ernst, Aurélie
TI  - Carbon ion radiotherapy eradicates medulloblastomas with chromothripsis in an orthotopic Li-Fraumeni patient-derived mouse model.
JO  - Neuro-Oncology
VL  - 23
IS  - 12
SN  - 1523-5866
CY  - Oxford
PB  - Oxford Univ. Press
M1  - DKFZ-2021-01184
SP  - 2028-2041
PY  - 2021
N1  - #EA:B420#LA:B420# / 2021 Dec 1;23(12):2028-2041
AB  - Medulloblastomas with chromothripsis developing in children with Li-Fraumeni Syndrome (germline TP53 mutations) are highly aggressive brain tumors with dismal prognosis. Conventional photon radiotherapy and DNA-damaging chemotherapy are not successful for these patients and raise the risk of secondary malignancies. We hypothesized that the pronounced homologous recombination deficiency in these tumors might offer vulnerabilities that can be therapeutically utilized in combination with high linear energy transfer carbon ion radiotherapy.We tested high-precision particle therapy with carbon ions and protons as well as topotecan with or without PARP inhibitor in orthotopic primary and matched relapsed patient-derived xenograft models. Tumor and normal tissue underwent longitudinal morphological (MRI), cellular (markers of neurogenesis and DNA damage-repair) and molecular characterization (whole-genome sequencing).In the primary medulloblastoma model, carbon ions led to complete response in 79
KW  - PARP inhibitor (Other)
KW  - carbon ion radiotherapy (Other)
KW  - chromothripsis (Other)
KW  - medulloblastoma (Other)
KW  - synthetic lethality (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:34049392
DO  - DOI:10.1093/neuonc/noab127
UR  - https://inrepo02.dkfz.de/record/169016
ER  -