Sox2 is an oncogenic driver of small-cell lung cancer and promotes the classic neuroendocrine subtype

Ellen Voigt, Madeline Wallenburg, Hannah Wollenzien, Ethan Thompson, Kirtana Kumar, Joshua Feiner, Moira McNally, Hunter Friesen, Malini Mukherjee, Yohannes Afeworki, Michael S. Kareta

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Although many cancer prognoses have improved in the past 50 years due to advancements in treatments, there has been little improvement in therapies for small-cell lung cancer (SCLC). One promising avenue to improve treatment for SCLC is to understand its underlying genetic alterations that drive its formation, growth, and cellular heterogeneity. RB1 loss is one key driver of SCLC, and RB1 loss has been associated with an increase in pluripotency factors such as SOX2. SOX2 is highly expressed and amplified in SCLC and has been associated with SCLC growth. Using a genetically engineered mouse model, we have shown that Sox2 is required for efficient SCLC formation. Furthermore, genome-scale binding assays have indicated that SOX2 can regulate key SCLC pathways such as NEUROD1 and MYC. These data suggest that SOX2 can be associated with the switch of SCLC from an ASCL1 subtype to a NEUROD1 subtype. Understanding this genetic switch is key to understanding such processes as SCLC progression, cellular heterogeneity, and treatment resistance.

Original languageEnglish (US)
Pages (from-to)2015-2025
Number of pages11
JournalMolecular Cancer Research
Issue number12
StatePublished - Dec 2021
Externally publishedYes

ASJC Scopus subject areas

  • General Medicine


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