Abstract

SCLC remains one of the most lethal lung cancers with limited therapeutic options. In recent years, we have made many advances on pathogenesis, heterogeneity and mechanism of resistance in SCLC. Increasing studies demonstrate that SCLC is a highly heterogeneous tumor. According to differentially expressed Neuroendocrine (NE) neuroendocrine, it can be divided into at least two categories, including NE and non-NE (or NE-low) subtypes. Charles M. Rudin and colleagues propose a novel method for SCLC subtypes defined by differential expression of key transcription regulators through integrating transcriptomic sequencing data. Each subtype has different clinicopathological characteristics. Cell line models in vitro demonstrate SCLC-A subtype is sensitive to BCL2 inhibitors, and SCLC-N subtype is highly sensitive to multiple Aurora Kinase (AURK) inhibitors. Besides, SCLC molecular subtypes exhibit distinct immunogenic feature, which could evoke varied responses to Immune Checkpoint Inhibitors (ICIs). Especially, POU2F3-expressing SCLC might origin from pulmonary tuft cells rather than neuroendocrine cells. And SCLC cells has enhanced plasticity and play an vital role in the cancer chemotherapy resistance and recurrence, and the mechanism underlying the cells plasticity has not yet been elucidated. It is vital to investigate the genetic characteristics of SCLC and their clinical significance. And our results provide some practical information. These advances are changing the clinical practices of SCLC.

Keywords: Small cell lung cancer; Neuroendocrine; Transcriptional subtyping; Cell plasticity; Genetic alteration