Embryonal tumor with multilayered rosettes (ETMR) is a rare and aggressive embryonal brain tumor that solely occurs in infants and young children and has only recently been recognized as a separate brain tumor entity in the WHO classification for CNS tumors. Patients have a very dismal prognosis with a median survival of 12 months upon diagnosis despite aggressive treatment. The aim of this study was to develop novel treatment regimens in a pre-clinical drug screen in order to inform potentially more active clinical trial protocols.
We have carried out an in vitro and in vivo drug screen using the ETMR cell line BT183 and its xenograft model. Furthermore, we have generated the first patient-derived xenograft (PDX) model for ETMR and evaluated our top drug candidates in an in vitro drug screen using this model.
BT183 cells are very sensitive to the topoisomerase inhibitors topotecan and doxorubicin, to the epigenetic agents decitabine and panobinostat, to actinomycin D, and to targeted drugs such as the PLK1 inhibitor volasertib, aurora kinase A inhibitor alisertib, and the mTOR inhibitor MLN0128. In xenograft mice, monotherapy with topotecan, volasertib, and actinomycin D, led to a temporarily response in tumor growth and a significant increase in survival. Finally, using multi-agent treatment regimens of topotecan or doxorubicin combined with methotrexate and vincristine the response in tumor growth and survival was further increased compared to mice receiving single treatments.
We have identified several promising candidates for combination therapies in future clinical trials for ETMR patients.
Pharmacology, Toxicology and Pharmaceutical Science
2
3%
Physics and Astronomy
2
3%
Other
7
10%
Unknown
23
34%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 2. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 15 August 2018.
All research outputs
#15,173,117
of 25,382,440 outputs
Outputs from Neuro-Oncology
#1,832
of 3,533 outputs
Outputs of similar age
#170,013
of 324,786 outputs
Outputs of similar age from Neuro-Oncology
#54
of 87 outputs
Altmetric has tracked 25,382,440 research outputs across all sources so far. This one is in the 38th percentile – i.e., 38% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 87 others from the same source and published within six weeks on either side of this one. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
