Current knowledge of small cell lung cancer transformation from non-small cell lung cancer

Semin Cancer Biol. 2023 Sep:94:1-10. doi: 10.1016/j.semcancer.2023.05.006. Epub 2023 May 26.

Abstract

Lung cancer is the leading cause of cancer related death, and is divided into two major histological subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Histological transformation from NSCLC to SCLC has been reported as a mechanism of treatment resistance in patients who received tyrosine kinase inhibitors (TKIs) targeting EGFR, ALK and ROS1 or immunotherapies. The transformed histology could be due to therapy-induced lineage plasticity or clonal selection of pre-existing SCLC cells. Evidence supporting either mechanism exist in the literature. Here, we discuss potential mechanisms of transformation and review the current knowledge about cell of origin of NSCLC and SCLC. In addition, we summarize genomic alterations that are frequently observed in both "de novo" and transformed SCLC, such as TP53, RB1 and PIK3CA. We also discuss treatment options for transformed SCLC, including chemotherapy, radiotherapy, TKIs, immunotherapy and anti-angiogenic agents.

Keywords: Heterogeneity; Lineage plasticity; NSCLC; SCLC; Transformation.

Publication types

  • Review

MeSH terms

  • Carcinoma, Non-Small-Cell Lung* / etiology
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • ErbB Receptors / genetics
  • Humans
  • Lung Neoplasms* / etiology
  • Lung Neoplasms* / genetics
  • Mutation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / therapeutic use
  • Proto-Oncogene Proteins / genetics
  • Small Cell Lung Carcinoma* / genetics
  • Small Cell Lung Carcinoma* / therapy

Substances

  • Protein-Tyrosine Kinases
  • ErbB Receptors
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins