Mechanistic understanding of how obesity causes cancer – Research project #2: How do physiological stressors affect the tumor ecosystem?

Obesity increases the risk of developing thirteen types of cancer that normal weight individuals may not develop despite of harbouring the same cancer risk loci. Globally, overweight/obesity may account for 544 300 cancer cases every year and is currently implicated in 15-20% of cancer-related mortalities. This places obesity second only to smoking as the most prevalent preventable cause of cancer.

We know that stem cells are intrinsically connected to the cellular niche in which they reside and that these cellular interactions are particularly important and instructive for stem cell plasticity. In this project we ask if an obese environment instructs the cancer stem cell niche to govern cancer cell dedifferentiation and enhanced stemness features.

AIM

The aims are to:

• Develop a comprehensive cellular spatial map of the cancer stem cell niche in obese and non-obese cancer patients.
• Comparatively extract obesity-dependent deregulated cell abundancies and cellular interactions within such niches.
• Mechanistically dissect the causal importance of the obesity-dependent niche composition.

APPROACH

Key methodologies for this project are spatial interrogation of the tumour microenvironments (sequencing and proteome-based), in vivo tumour modelling and antibody-based therapeutics.