Abstract

During tumour development and upon therapy, cancer cells flexibly switch between proliferation and cell cycle arrest to adapt to intrinsic and extrinsic stress. How these plastic switches are governed in the context of constrained cancer evolution trajectories and of the tumour microenvironment remains poorly understood. In this talk, I will discuss recent insights we have obtained from bulk, single cell and spatial transcriptomics datasets into the genomic constraints and gene regulatory programmes shaping proliferation and cell cycle arrest switches in cancer. We use large language models applied to single cell data and methods inspired from ecology applied to spatial transcriptomics to identify and characterise a G0 arrested, hybrid EMT state with hallmarks of unfolded protein response stress, defining an immune evasive and plastic niche which could be relevant for immunotherapy. Our methods, EMT -LM and SpottedPy, can be flexibly applied to classify and characterise plastic cell states and their microenvironmental niches in cancer.