Nicola Aceto

Single cell-resolution parallel exome and transcriptome analysis of human circulating tumor cells

Cancer patients that develop a metastatic disease are currently considered incurable. Mainly, this is due to a limited understanding of the molecular mechanisms that characterize the metastatic process, and the lack of effective metastasis-suppressing agents. The metastatic cascade begins with primary tumor cells entering the blood circulation, and it is followed by their extravasation at distant sites, where they form proliferative metastatic lesions. Cancer cells in circulation are referred to as circulating tumor cells (CTCs), and their isolation has been hampered for many years by technological constraints. However, CTC isolation and characterization has recently become possible, and it has revealed highly unexpected features of the metastatic process. For instance, using a combination of microfluidic and robotic technologies, single cell sequencing, molecular and computational biology, we understood that CTC-clusters, rather than single migratory CTCs, are highly efficient metastatic precursors in breast and prostate cancer. Our research now focuses on the identification of the vulnerabilities of CTC-clusters, adopting methods such as single cell parallel exome and transcriptome sequencing, with the ultimate goal of developing metastasis-suppressing agents.