Characterising and harnessing Tumour/Stroma interactions to improve treatment of metastatic colorectal cancer

This study will use a new integrated tissue culture platform that enables the join-culture of multiple cell types under conditions that mimic organ blood flow in vivo.

Places available:

  • One Master of Biomedical Science
  • One Honours

The plasticity of tumour cell phenotypes impacts on their drug resistance ability and is influenced by the tumour microenvironment. Indeed, tumour cell phenotype is under constant remodelling under the competing pressure of intrinsic/hardwired (eg genetic) signals and of environmental effectors such as stomal and immune cells, non-cellular matrix components, biophysical parameters (eg density, stiffness). In the context of cancer metastasis, tumour cells must deal with very different environmental conditions compared to what they had to face in their organ of origin.

Integrated knowledge of the contributions by intrinsic and extrinsic effectors in shaping intra-tumour heterogeneity would improve our understanding of tumour progression and allow the team to determine the impact of each component in treatment response.

In this project, to better mimic the interactions between different cell types within metastatic tumours, a new integrated tissue culture platform will be used that enables the join-culture of multiple cell types under conditions that mimic organ blood flow in vivo. Patient-derived tumour organoids with known genomic profile will be jointly grown with hepatocytes, cancer-associated fibroblasts, and/or immune cells to dissect how individual stromal cell types affect the phenotype of metastatic cells, and to identify mechanisms that could be harnessed to reinstate an anti-metastasis immune response. This will be performed in the presence of standard of care treatment and of a novel targeted drug, allowing the team to infer the impact of tumour/stromal interactions on treatment response in metastatic disease.

This project will involve varied techniques such as 3D tissue coculture, flow cytometry, immunostaining, cellular barcoding and sequencing. Expected outcomes will open the door for novel therapeutic strategies combining targeted drugs and/or immunotherapy for the benefit of patients with metastatic colorectal cancer.

Contact and more information

Professor Frederic Hollande