CHK1 inhibition in small-cell lung cancer produces single-agent activity in biomarker-defined disease subsets and combination activity with cisplatin or olaparib

Effective targeted therapies for small-cell lung cancer (SCLC), cisplatin or the PARP inhibitor olaparib, and improved the the most aggressive form of lung cancer, remain urgently response of platinum-resistant models. Proteomic analysis needed. Here we report evidence of preclinical efficacy evoked identified CHK1 and MYC as top predictive biomarkers of by targeting the overexpressed cell-cycle checkpoint kinase LY2606368 sensitivity, suggesting that CHK1 inhibition may CHK1 in SCLC. Our studies employed RNAi-mediated atten-be especially effective in SCLC with MYC amplification or MYC uation or pharmacologic blockade with the novel second-protein overexpression. Our findings provide a preclinical generation CHK1 inhibitor prexasertib (LY2606368), currently proof of concept supporting the initiation of a clinical efficacy in clinical trials. In SCLC models in vitro and in vivo, LY2606368 trial in patients with platinum-sensitive or platinum-resistant exhibited strong single-agent efficacy, augmented the effects of relapsed SCLC.