Stalling the replication fork via the impedimental stabilization of higher-order dnas
Cancer is a generic term for a group of diseases characterized by the uncontrolled growth and spread of cells with abnormal proliferating activity. Most of the anticancer drugs currently used in the clinic trigger irreversible DNA damages and thus, promote replicative stress. As an alternative of irreversible DNA strand breaks, the non-covalent small-molecule stabilization of unusual, non-B DNA structures has emerged as a promising way to create DNA damages. One of such non B-DNA structures is a three-way DNA junction that might fold both upstream and downstream of the replication fork. The stabilization of three-way junctions by small molecules therefore opens a promising way to induce replicative stress in a highly cancer-specific manner. The main goal of the project ""STARFISH DNA"" (for ""Stalling the Replication Fork via the Impedimental Stabilization of Higher-order DNAs"") is to identify a new series of compounds capable of creating DNA damages through three-way junction stabilization and to use them either as standalone therapeutic agent to fight against cancers or in combination with established drugs that disrupt cancer signaling pathways in a synergistic manner.