Preclinical Modelling
Developing a 3-tier strategy using cell culture, 3D bio-systems (organoids, bioprinting), and in vivo models to study brain cancer pathogenesis.
WG2. Preclinical Modelling
175
No of members
Dr Anna Golebiewska
WG Leader
Dr Barbara Breznik
WG Co-Leader
Clinical Research
Category
PRECLINICAL MODELS (Theme-2): Development of more accurate genetically engineered mouse models (GEMMs), and patient-derived orthotopic xenografts models (PDOXs), as well as 3D Systems (neurosphere, organoids and bioprinting) should contribute to a better understanding of brain tumour mechanisms.
This Action also aims to explore the use of advanced 4D intravital microscopy methods to study the response of brain cancer cells in GEMMs and PDOXs to innovative therapies at the single-cell level in their native environment. The CRISPR/Cas9 technology will be applied both in vitro and in vivo, to model the most frequent genetic alterations (e.g., EGFR, TP53, APOBEC) and to study their contribution to treatment response.
Moreover, by combining optical access to the brain tumour using a cranial imaging window and multiphoton microscopy, the cellular response and resistance to therapy can be followed inside the living animal. Spatial transcriptomics will be carried out to investigate cell-to-cell variation within and between individual tumours. Advanced 3D cerebral organoids and bioprinting-based brain tumour models will be used to study vulnerabilities and drug resistance, including in vitro blood-brain tumour barrier (BBTB) models to better understand chemoresistance.
Objectives
To design advanced pre-clinical models to reveal the pathogenesis of brain cancer. Relevant to RCO2 and RCO3.
Tasks
T2.1 Improve preclinical modelling (new animal models, organoids, 3D models, bio-printed scaffolds); T2.2 Improve single cell techniques for patient stratification; T2.3 WG2 meetings.
Activities
Involved in all MC and WG2 meetings including organizing a WG2/WG3-focused conference, contributing to annual and final reports, publications, dissemination, exploitation, and training schools.
Milestones
M2.1: WG2/WG3 conference in month 22; M2.2: Mid-term report in month 25.