In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 22, No. 16_Supplement ( 2016-08-15), p. A25-A25
Abstract:
Solid tumors of the nervous system are the most common childhood cancers after leukemias. Although brain tumors are the leading cause of cancer-related mortality in children, there are not enough adequate model systems to study their biology. We therefore started a pediatric preclinical testing program in Heidelberg to generate orthotopic patient-derived xenograft (PDX) models for a large variety of pediatric brain tumors. Freshly dissected primary material from multiple centers is being sent to us immediately after surgical resections. One part of the tumor is being reserved for pathological and molecular analysis and the other part is being dissociated into a single cell suspension and injected into the brain of immunodeficient mice. After successful engraftment and passaging, extensive molecular characterization of the PDX tumor and the matching primary tumor are being performed. Thus far, we have injected 95 tumors: 36 low-grade gliomas (LGG), 23 medulloblastomas (MB), 13 ependymomas (EPN), 7 high-grade gliomas (HGG), 6 atypical teratoid rhaboid tumors (AT/RT), 3 meningeal tumors (MT), 3 embryonal tumors with multilayered rosettes (ETMR), 2 gliomatosis cerebri (GC), 1 dysembryoplastic neuroepithelial tumor (DNT) and 1 primitive neuroectodermal tumor (PNET). No engraftment was observed for any of the low-grade tumors (LGG, MT, DNT). For high-grade tumors we established initial engraftments of MB (5/23, 22%), EPN (5/13, 38%), HGG (2/7, 29%), AT/RT (2/6, 33%), ETMR (1/3, 33%) and PNET (1/1, 100%). 11 out of 16 (69%) established PDX models were already passaged at least twice in mice and can be used for preclinical experiments. We conclude that it is possible to generate preclinical models for most malignant pediatric brain tumor entities, but not for low-grade tumors using our current protocol. However, even for the malignant entities there seems to be a selection for only the most aggressive subtypes that successfully engraft. Therefore, due to the low engraftment rate of some tumor types, the rarity of pediatric brain tumors and the multitude of different subtypes, international collaborations are absolutely necessary in this field in order to generate and characterize a broad repertoire of PDX models for all pediatric brain tumor subtypes for preclinical testing. Citation Format: Norman L. Mack, Sebastian Brabetz, Florian Selt, Xanthopolous Christina, David Sumerauer, Heidi Bächli, Arnulf Pekrun, Martin U. Schuhmann, Stefan M. Pfister, Olaf Witt, Till Milde, Marcel Kool. Establishment of orthotopic patient-derived xenograft models of pediatric brain tumors – the Heidelberg experience. [abstract]. In: Proceedings of the AACR Special Conference: Patient-Derived Cancer Models: Present and Future Applications from Basic Science to the Clinic; Feb 11-14, 2016; New Orleans, LA. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(16_Suppl):Abstract nr A25.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1557-3265.PDX16-A25
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2016
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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