Development of solid tumours is accompanied by invasion and metastasis, the major cause of cancer-related mortality. Cytotoxic drugs typically provide only partial control of solid cancer and do not prevent metastasis. Specific targeting of cancer cell invasiveness to prevent tumour dissemination is thus highly warranted. We have established the migrastatics concept – a use of drugs suppressing cancer cell invasiveness to prevent metastasis without necessarily affecting tumour growth. In this project we aim to identify potential migrastatics among drugs already approved even for cancer-unrelated indications. The potential migrastatics chosen based on published results and mechanistic rationale will be tested in 3D invasion setup using a semi-automated spheroid-based screening system. We will then examine the selected compounds with further cell invasion and other assays to found those with favourable efficacy /toxicity profiles. Finally, we will verify the migrastatic effects of the best candidate drugs in primary human cancer cells and in vivo in mouse models of cancer metastasis.

Klíčová slova
migrastatics, anti-cancer thereapy, invasiveness, metastasizing, drug repurposing