Neuroendocrine negative SCLC is mostly RB1 WT and may be sensitive to CDK4/6 inhibition

Abstract Small cell lung cancer (SCLC) is an aggressive form of lung cancer with limited therapeutic options, a very high mortality rate and is characterized, in most cases, by neuroendocrine features. A small but important subset of SCLC has intact RB1. However, other characteristics of this subset are not well-defined. To comprehensively assess the underlying genomics of SCLC cell lines with functional RB1, we examined 48 SCLC cell lines from the Cancer Cell Line Encyclopedia (CCLE) collection. Out of these 48 SCLC cell lines, 8 were found to be RB1 WT. We found that RB1 WT SCLC lines are enriched for loss of neuroendocrine lineage markers with CDKN2A inactivation, or CCND1 amplification. Six RB1 WT SCLC cell lines were included in NCI SCLC drug sensitivity screen and two of them were sensitive to CDK4/6 inhibition.