Harnessing Small Molecules for Revealing Vulnerabilities in Circulating Tumor Cells.

Breast cancer is among the most commonly diagnosed cancers, accounting for 685,000 fatalities in 2020 worldwide. High mortality rate is associated with the development of metastases, a complex process involving the spread of cancer cells from the primary tumor site to secondary organs. At present, treating patients with metastatic disease is challenging, and this still represent an unmet medical need. As clinically-relevant models, circulating tumor cell (CTC)-derived models can serve as a drug screen platforms that enable drug susceptibility testing and discovery of novel compounds with anti-cancer progression activity. Here, by employing a combination of CTC-based drug screening platform, in vivo models of metastatic breast cancer, RNA sequencing, and in vitro cell assays, we identified new agents for the reduction of tumor growth and lung colonization in breast cancer. Furthermore, our transcriptomic data delineate the metastasis-relevant signaling pathways affected by these treatments. Overall design: Cells were treated with either a control vehicle (0.25% DMSO) or 5 µM of above mentioned component for 2h and 6h, respectively. Total RNA was extracted using the RNeasy Mini Kit (Qiagen) as per the manufacturer's instructions for sequencing.