Dynamic variations in epithelial-to-mesenchymal transition (EMT), ATM, and SLFN11 govern response to PARP inhibitors and cisplatin in small cell lung cancer.

ABSTRACT: Small cell lung cancer (SCLC) is one of the most aggressive forms of cancer, with a 5-year survival <7%. A major barrier to progress is the absence of predictive biomarkers for chemotherapy and novel targeted agents such as PARP inhibitors. Using a high-throughput, integrated proteomic, transcriptomic, and genomic analysis of SCLC patient-derived xenografts (PDXs) and profiled cell lines, we identified biomarkers of drug sensitivity and determined their prevalence in patient tumors. In contrast to breast and ovarian cancer, PARP inhibitor response was not associated with mutations in homologous recombination (HR) genes (e.g., BRCA1/2) or HRD scores. Instead, we found several proteomic markers that predicted PDX response, including high levels of SLFN11 and E-cadherin and low ATM. SLFN11 an

SUBMITTER: Allison Stewart C 

PROVIDER: S-EPMC5438673 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature