Philipp Altrock

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  Short Talk: Tumor growth and clonal heterogeneity during expansion and treatment
  Philipp Altrock

  Cancers arise through a process of somatic evolution. This evolutionary process can result in substantial clonal heterogeneity. The mechanisms responsible for the coexistence of distinct clonal lineages and the biological consequences of this coexistence remain poorly understood. Based on in vivo data from a mouse xenograft model, we investigate the influence of clonal heterogeneity on tumor properties, and mathematically model competitive expansion of individual clones. We find that tumor growth can be driven by a minor cell subpopulation. This minor population of cells enhances the proliferation of all cells within a tumor by overcoming environmental constraints. Yet, this driving cell population can be outcompeted by faster proliferating competitors. This can result in tumor collapse. We describe how that non-cell autonomous driving of tumor growth supports clonal interference, stabilizes clonal heterogeneity and enables inter-clonal interactions, which can lead to new phenotypic tumor traits. When treatment is administered, heterogeneity can be reduced, also reducing evolutionary and metastatic potential. We adjust and inform our mathematical framework to model different treatment strategies and optimize treatment processes, in particular in HER2+ breast cancer tumors.