Origins, genetic landscape, and emerging therapies of small cell lung cancer

Genes Dev. 2015 Jul 15;29(14):1447-62. doi: 10.1101/gad.263145.115.


Lung cancer is the leading cause of cancer deaths, with small cell lung cancer (SCLC) representing the most aggressive subtype. Standard treatments have not changed in decades, and the 5-year survival rate has remained <7%. Genomic analyses have identified key driver mutations of SCLC that were subsequently validated in animal models of SCLC. To provide better treatment options, a deeper understanding of the cellular and molecular mechanisms underlying SCLC initiation, progression, metastasis, and acquisition of resistance is required. In this review, we describe the genetic landscape of SCLC, features of the cell of origin, and targeted therapeutic approaches.

Keywords: GEMM; SCLC; cell of origin; driver; neuroendocrine; targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Disease Models, Animal
  • Drug Resistance, Neoplasm
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Mutation
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Small Cell Lung Carcinoma / therapy*


  • Antineoplastic Agents