Project Details
Description
In the framework of the phase I Neuro immunotherapy project, funded by Kriibskrank Kanner Foundation, we evaluated the impact of JQ1 drug on Neuroblastoma tumor using TH-MYCN spontaneous mouse model. The TH-MYCN model, developed by Weiss and al, is a highly relevant model representative of high-risk NB in child. Indeed the histology and the genetic alterations observed in this model are similar to those seen in the human disease. JQ1 (Jun Qi 1) is a small molecule binds to BRD4 protein, a member of the bromodomain and extra-terminal (BET) family of transcription factors. Such binding prevents the interaction of BRD4 with the acetylated lysine residues within chromatin, and subsequently blocks the recruitment of positive transcription elongation factor (P-TEFb) and other super enhancers involved in transcription of downstream genes including the best-characterized oncogenic marker of risk in neuroblastoma MYCN. JQ1 has been used in pre-clinical neuroblastoma mouse models and demonstrated significant efficacy in enhancing survival. In addition to NB, JQ1 has shown an anti-tumor activity in other pre-clinical models of childhood sarcoma by suppressing the secretion of angiogenic factors by tumor cells and subsequently blocking the angiogenesis driven by VEGF. In these preclinical models, it has been reported that JQ1 treatment stabilized the tumor progression, rather than reduced the tumor volume, indicating that the therapeutic efficacy of JQ1 needs to be improved. Furthermore, JQ1 also showed promising pre-clinical results in other pediatric malignancies such as medulloblastoma and hematological malignancies
Acronym | NEUROIMMUNOTHERAPY PHASE II |
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Status | Finished |
Effective start/end date | 1/07/19 → 30/06/23 |
Funding
- Fondatioun Kriibskrank Kanner: €136,000.00
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