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

为了开发新的辅助疗法来预防早期转移集落的形成和根除潜在的转移奠基者，了解播散性癌细胞（DCCs）的遗传、表观遗传和功能武装是至关重要的。在项目A01中，我们将通过三步方法来解决这个问题。首先，我们将建立从m0期疾病进展到m1期疾病的患者纵向采集样本的细胞谱系树。我们将确定位于细胞谱系树转移分支最接近根部的DCC，并进行详细的遗传表征。其次，我们将挖掘dcc的转录组和基因组，以确定与早期转移定植相关的分子机制。第三，我们将开发具有代表性的转移创始细胞模型，用于功能评估和治疗靶向。

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.