Killing SCLC: insights into how to target a shapeshifting tumor.

Journal Article (Journal Article;Review)

Small cell lung cancer (SCLC) is a rapidly growing, highly metastatic, and relatively immune-cold lung cancer subtype. Historically viewed in the laboratory and clinic as a single disease, new discoveries suggest that SCLC comprises multiple molecular subsets. Expression of MYC family members and lineage-related transcription factors ASCL1, NEUROD1, and POU2F3 (and, in some studies, YAP1) define unique molecular states that have been associated with distinct responses to a variety of therapies. However, SCLC tumors exhibit a high degree of intratumoral heterogeneity, with recent studies suggesting the existence of tumor cell plasticity and phenotypic switching between subtype states. While SCLC plasticity is correlated with, and likely drives, therapeutic resistance, the mechanisms underlying this plasticity are still largely unknown. Subtype states are also associated with immune-related gene expression, which likely impacts response to immune checkpoint blockade and may reveal novel targets for alternative immunotherapeutic approaches. In this review, we synthesize recent discoveries on the mechanisms of SCLC plasticity and how these processes may impinge on antitumor immunity.

Full Text

Duke Authors

Cited Authors

  • Sutherland, KD; Ireland, AS; Oliver, TG

Published Date

  • March 1, 2022

Published In

Volume / Issue

  • 36 / 5-6

Start / End Page

  • 241 - 258

PubMed ID

  • 35318269

Pubmed Central ID

  • PMC8973850

Electronic International Standard Serial Number (EISSN)

  • 1549-5477

Digital Object Identifier (DOI)

  • 10.1101/gad.349359.122


  • eng

Conference Location

  • United States