Mutations in tumours can serve as markers that allow tracking of past evolution from current samples but also provide insights into future dynamics. In this talk, I present two limiting cases: The first case is a collaboration with the Weghorn lab where we explore the spatio-temporal dynamics of early tumours. We leverage published data from resected hepatocellular carcinomas, each with several hundred samples taken in two and three dimensions. Using spatial metrics of evolution, we find that tumour cells grew predominantly uniformly within the tumour volume rather than at its boundary. We examine how mutations and cells are dispersed throughout the tumour and how cell death contributes to the overall tumour growth. The second case focuses on late tumour evolution under molecularly targeted therapy. In practice, targeted therapy is severely limited by the expansion of therapy-resistant mutants which typically preexist at the start of treatment. How many distinct resistance mechanisms can be found in a realistically-sized population of tumour cells? And can all of them be treated upfront by a suitable combination therapy? An answer is provided for a cell-line model of non-small cell lung cancer.

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