Small cell lung cancer (SCLC) is a highly aggressive form of lung cancer and is one of the most lethal human malignancies. It is characterised by rapid growth and early development of metastasis. First line treatment for SCLC consists of a chemotherapy doublet of cisplatin or carboplatin in combination with etoposide. Up to 80% of patients respond to first line therapy, however, most patients relapse with a chemoresist recurrence resulting in a dismal overall 5-year survival rate of <5%.
We performed a bioinformatic analysis of large publicly available datasets to identify genetic predictors for carboplatin resistance or sensitivity in SCLC. Cell line carboplatin sensitivity data retrieved from the Cancer Target Discover and Development (CTD2) database was correlated with their corresponding gene expression profiles from the Cancer Cell Line Encyclopaedia (CCLE). The analysis was performed across all available cancer cell lines (799 cell lines) as well as lung cancers only (137 cell lines). 1231 genes significantly correlate with increased resistance to carboplatin therapy (p<0.05). Gene ontology analysis of carboplatin resistance associated genes show an enrichment for DNA replication, base excision repair and the T-cell receptor signalling pathway. We performed Spearman correlation analysis of the carboplatin resistance gene set with survival in a cohort of 45 platinum naive SCLC patient which showed that 22 genes were significantly associated with both carboplatin resistance and poor patient survival.