Molecular subtypes of small cell lung cancer: a synthesis of human and mouse model data

Charles M. Rudin, John T. Poirier, Lauren Averett Byers, Caroline Dive, Afshin Dowlati, Julie George, John V. Heymach, Jane E. Johnson, Jonathan M. Lehman, David MacPherson, Pierre P. Massion, John D. Minna, Trudy G. Oliver, Vito Quaranta, Julien Sage, Roman K. Thomas, Christopher R. Vakoc, Adi F. Gazdar

Research output: Contribution to journalReview articlepeer-review

453 Scopus citations


Small cell lung cancer (SCLC) is an exceptionally lethal malignancy for which more effective therapies are urgently needed. Several lines of evidence, from SCLC primary human tumours, patient-derived xenografts, cancer cell lines and genetically engineered mouse models, appear to be converging on a new model of SCLC subtypes defined by differential expression of four key transcription regulators: achaete-scute homologue 1 (ASCL1; also known as ASH1), neurogenic differentiation factor 1 (NeuroD1), yes-associated protein 1 (YAP1) and POU class 2 homeobox 3 (POU2F3). In this Perspectives article, we review and synthesize these recent lines of evidence and propose a working nomenclature for SCLC subtypes defined by relative expression of these four factors. Defining the unique therapeutic vulnerabilities of these subtypes of SCLC should help to focus and accelerate therapeutic research, leading to rationally targeted approaches that may ultimately improve clinical outcomes for patients with this disease.

Original languageEnglish (US)
Pages (from-to)289-297
Number of pages9
JournalNature Reviews Cancer
Issue number5
StatePublished - May 1 2019

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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