查看文章

Background: Small cell lung cancer (SCLC) is the most aggressive form of lung cancer, accounting for 14% of lung cancers. It is associated with poor outcomes and few effective treatments. Identification of novel therapeutic targets is imperative for improving treatment outcomes. In our previous work we identified several DNA repair proteins including check point kinase 1 (Chk1) and poly (ADP-ribose) polymerase 1 (PARP1) that are overexpressed in SCLC and are high priority candidate targets. TP53-mutant cells (a hallmark of SCLC) rely on Chk1 to arrest the S and G2 phases of the cell cycle. Hence, inhibition of Chk1 in p53 mutant cells abrogates the S and G2 checkpoints driving such cells to mitotic catastrophe and apoptosis. In this study we tested the in vitro efficacy of Chk1 inhibitors as single agents and in combination with a PARP1 inhibitor and cisplatin.

Experimental design: SCLC cell lines [human cell …