Despite the great progress that has been made in treating cancer, metastasis remains incurable. Metastasis accounts for 8 million deaths per year worldwide and no agents are currently available to prevent the metastatic spread of cancer. The metastatic process begins with cancer cells leaving the primary tumor site and entering the blood circulation. In circulation, cancer cells are defined as circulating tumor cells (CTCs), and are typically found in the form of single CTCs or small CTC aggregates (CTC clusters). Upon dissemination and survival into distant organs, cancer cells give rise to proliferating metastatic lesions, which in turn can shed other CTCs and form additional metastases. While virtually all oncology-related drugs aim to kill cancer cells within a tumor, no drugs are available to target metastatic cells in circulation. As a consequence, no drugs are available to block or prevent the metastatic cascade.
We recently discovered that CTC clusters are exceptionally efficient metastatic precursors, capable to initiate a metastasis 50-times better than single CTCs. Within our ERC Starting Grant Project Holding-Hands, through a screen with 2’456 FDA-approved compounds, we discovered those that enable the disaggregation of CTC clusters in breast cancer mouse models and consequently, lead to metastasis suppression. This exciting new discovery implies that targeting CTC clusters is now feasible, and that this approach is likely to delay or prevent metastasis formation in cancer patients. Thus, within this Proof of Concept application, we aim to screen and patent additional cluster-targeting compounds with higher efficacy and better safety profile, to establish a new company whose aim is to commercialize cluster-targeting molecules, and to prepare for clinical trials.
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