Figure 2.

Landscape of predictive biomarkers in SCLC. Recent preclinical studies identified predictive biomarkers of response to DDR-targeted therapies in SCLC. SLFN11 predicts sensitivity to PARP inhibitors and chemotherapy; AXL and/or EMT predict resistance to PARP and WEE1 targeting; high ATM expression predicts resistance to PARP and ATR-targeted therapies; high MYC expression and amplification predicts sensitivity to AURK and CHK1 inhibitors; high expression of the inhibitory Notch ligand Delta-like protein 3 (DLL3) predicts response to Rovalpituzumab tesirine, a DLL3-targeted antibody-drug conjugate. Approximate proportions for each biomarker are estimated based on a combination of reported patient tumor and/or patient-derived xenograft expression and (where available) response rates in specific biomarker-selected populations [DLL3 (PMID: 27932068), MYC (PMID: 28490518), SLFN11/ATM/EMT (PMID: 28212573)]. For example, while >50% DLL3 expression was noted in in over two-thirds of evaluated patient samples, an objective response was observed in only 18% of evaluable patients, suggesting proportion of SCLC sensitive to DLL3 is less than that which expresses high DLL3 (PMID: 27932068). SCLC, small cell lung cancer; SLFN11, schlafen 11; PARP, poly-ADP-ribose polymerase; DDR, DNA damage response; EMT, epithelial-mesenchymal transition; ATM, ataxia telangiectasia-mutated; ATR, ataxia telangiectasia and Rad3-related protein; AURK, Aurora kinase; CHK1, checkpoint kinase 1; PDX, patient-derived xenograft.