RB loss in resistant EGFR mutant lung adenocarcinomas that transform to small-cell lung cancer.

Nat Commun
Publication type
Journal Article
Authors
Keywords
Abstract

Tyrosine kinase inhibitors are effective treatments for non-small-cell lung cancers (NSCLCs) with epidermal growth factor receptor (EGFR) mutations. However, relapse typically occurs after an average of 1 year of continuous treatment. A fundamental histological transformation from NSCLC to small-cell lung cancer (SCLC) is observed in a subset of the resistant cancers, but the molecular changes associated with this transformation remain unknown. Analysis of tumour samples and cell lines derived from resistant EGFR mutant patients revealed that Retinoblastoma (RB) is lost in 100% of these SCLC transformed cases, but rarely in those that remain NSCLC. Further, increased neuroendocrine marker and decreased EGFR expression as well as greater sensitivity to BCL2 family inhibition are observed in resistant SCLC transformed cancers compared with resistant NSCLCs. Together, these findings suggest that this subset of resistant cancers ultimately adopt many of the molecular and phenotypic characteristics of classical SCLC.

Year of Publication
2015
Journal
Nat Commun
Volume
6
Pages
6377
Date Published
2015 Mar 11
ISSN
2041-1723
URL
DOI
10.1038/ncomms7377
PubMed ID
25758528
PubMed Central ID
PMC4357281
Links
Grant list
P50CA090578 / CA / NCI NIH HHS / United States
R01 CA137008 / CA / NCI NIH HHS / United States
R01CA137008 / CA / NCI NIH HHS / United States
P30 CA008748 / CA / NCI NIH HHS / United States
P50 CA090578 / CA / NCI NIH HHS / United States
R21 CA156000 / CA / NCI NIH HHS / United States
5R21CA156000 / CA / NCI NIH HHS / United States