Small-cell lung cancer: what we know, what we need to know and the path forward

Nat Rev Cancer. 2017 Dec;17(12):725-737. doi: 10.1038/nrc.2017.87. Epub 2017 Oct 27.


Small-cell lung cancer (SCLC) is a deadly tumour accounting for approximately 15% of lung cancers and is pathologically, molecularly, biologically and clinically very different from other lung cancers. While the majority of tumours express a neuroendocrine programme (integrating neural and endocrine properties), an important subset of tumours have low or absent expression of this programme. The probable initiating molecular events are inactivation of TP53 and RB1, as well as frequent disruption of several signalling networks, including Notch signalling. SCLC, when diagnosed, is usually widely metastatic and initially responds to cytotoxic therapy but nearly always rapidly relapses with resistance to further therapies. There were no important therapeutic clinical advances for 30 years, leading SCLC to be designated a 'recalcitrant cancer'. Scientific studies are hampered by a lack of tissue availability. However, over the past 5 years, there has been a worldwide resurgence of studies on SCLC, including comprehensive molecular analyses, the development of relevant genetically engineered mouse models and the establishment of patient-derived xenografts. These studies have led to the discovery of new potential therapeutic vulnerabilities for SCLC and therefore to new clinical trials. Thus, while the past has been bleak, the future offers greater promise.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Humans
  • Mice
  • Molecular Targeted Therapy*
  • Neurosecretory Systems / metabolism
  • Receptors, Notch / genetics
  • Retinoblastoma Binding Proteins / genetics
  • Signal Transduction
  • Small Cell Lung Carcinoma / drug therapy*
  • Small Cell Lung Carcinoma / genetics*
  • Small Cell Lung Carcinoma / pathology
  • Tumor Suppressor Protein p53 / genetics
  • Ubiquitin-Protein Ligases / genetics
  • Xenograft Model Antitumor Assays


  • RB1 protein, human
  • Receptors, Notch
  • Retinoblastoma Binding Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Ubiquitin-Protein Ligases