Xiao Fu

Evolutionary and ecological principles shape tumour development and treatment resistance. In this talk, I will introduce our previous work on modelling the evolutionary dynamics of tumours and then present two ongoing projects in the lab to unravel the ecological interactions that shape tumour growth patterns and sculpt the tumour microenvironment. In the context of colorectal cancer liver metastasis, we employed generalised Lotka-Volterra models to describe the interactions between cancer cells, hepatocytes, and fibroblasts, and identified alternative stable states reminiscent of distinct metastatic growth patterns and parameter conditions governing transitions between these states. Leveraging single-cell transcriptomics, we further examined cellular and molecular mechanisms underlying the ecological principles. In the context of pancreatic cancer, we performed multi-parametric feature analysis to quantify the spatial organisation of cancer cells and cancer-associated fibroblasts (CAFs) in single-cell spatial transcriptomics. This analysis revealed that several tumour architectural features are associated with phenotypic heterogeneity of CAFs. Through a reductionist agent-based model (ABM) encoding interactions between cancer cells and CAFs, we demonstrated that spatial and biophysical factors can influence phenotypic evolution of CAFs and provided a parsimonious mechanistic interpretation for observations in the snapshot spatial data. Together, through integrative mapping and modelling approaches, our work aims to decipher organisational principles of the tumour ecosystem and identify novel strategies, through the lens of eco-evolutionary dynamics, to better intercept and treat cancer.