Evolution of systemic cancer: Mapping the acquisition of metastatic traits into cell lineage trees (A01)

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For the development of novel adjuvant therapies to prevent early metastatic colony formation and to eradicate candidate metastasis founders, it is essential to understand the genetic, epigenetic and functional armament of disseminated cancer cells (DCCs). In project A01, we will address this by a three-step approach. Firstly, we will establish cell lineage trees of longitudinally collected samples from patients progressing from M0-stage disease to M1-stage disease. We will identify the DCC(s) located closest to the root of the metastatic branch of the cell lineage tree and perform detailed genetic characterisation. Secondly, we will mine the transcriptomes and genomes of DCCs to identify molecular mechanisms associated with early metastatic colonisation. Thirdly, we will develop cellular models representative of metastasis founders for functional evaluation and therapeutic targeting.