WP4 – Pre-clinical drug-testing in vivo model systems

Rationale 

Several studies have shown that the cancer model choice is crucial for the translation of research findings into clinical practice. Commercially available, stable cell lines do not recapitulate many of the properties of a patient’s tumours, prompting the development of primary spheroid culture models and xenograft models in immunocompromised mice.

Feasibility

The Erler lab has extensive experience in culturing GBM patient-derived stem cell organoids and orthotopic tumours (Perryman, Høye et al, Neuro-Oncology, under revision). Furthermore, Prof Erler and Prof Lassen co-lead a successful precision medicine program for patients with metastatic solid tumours funded by the Innovationsfonden.

Objectives

• Establishment of in vitro organoid cultures and an in vivo PDX model for every tumour
  
• Pre-clinical testing of available inhibitors of these targets in vitro and in vivo
  

Endpoints

Patient-derived organoid (PDO) cultures established and growing sufficiently to enable drug screening. Drug screens will be repeated until an effective therapy is identified, using molecular information as a guide.

Mice with patient-derived xenograft (PDX) tumours showing clinical signs of cancer will be terminated at humane endpoints, according to license permission, for biobanking and histological analysis.

Expected impact

Molecular analysis combined with functional testing has been shown to greatly improve patient tumour response, quality of life (QoL) and progression-free survival (PFS).
We therefore expect to significantly impact GBM patient response, QoL and PFS.
We will develop highly useful reagents for the research field (PDOs and PDXs), as well as possibly identify novel therapeutic strategies for GBM patient treatment.