prexasertib + topotecan

Prexasertib + topotecan is an investigational combination therapy being evaluated for the treatment of advanced solid tumors, including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Prexasertib is a potent, selective small molecule inhibitor of checkpoint kinase 1 (CHK1), a key regulator of the DNA damage response (DDR) that mediates cell cycle arrest and DNA repair. Topotecan is a cytotoxic chemotherapy agent that inhibits DNA topoisomerase I, leading to the formation of stable cleavable complexes and subsequent double-strand DNA breaks during replication. The rationale for this combination lies in the synergistic enhancement of DNA damage; topotecan induces genomic instability, while prexasertib abrogates the CHK1-dependent S and G2/M checkpoints, forcing cells with damaged DNA into premature mitosis and apoptosis. This approach is particularly targeted at tumors with high replication stress or defects in other DDR pathways, such as TP53 mutations. While originally developed by Eli Lilly, prexasertib is currently being advanced by Acrivon Therapeutics.

Other names

LY2606368 + topotecanACR-368 + topotecan