Format

Send to

Choose Destination
Nat Commun. 2015 Mar 11;6:6377. doi: 10.1038/ncomms7377.

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

Author information

1
1] Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA [2] Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
2
Memorial Sloan Kettering Cancer Center, Thoracic Oncology Service, 1275 York Avenue, New York, New York 10065, USA.
3
1] Broad Institute of MIT and Harvard, Cancer Genome Comparative Analysis Group, 415 Main Street, Cambridge, Massachusetts 02142, USA [2] Department of Pathology, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, Massachusetts 02114, USA.
4
1] Department of Pathology, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, Massachusetts 02114, USA [2] Department of Pathology, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA.
5
1] Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [2] Molecular Profiling Laboratory, Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA.
6
Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02115, USA.
7
Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts 02115, USA.
8
1] Department of Medical Oncology, Belfer Institute of Applied Science, Dana Farber Cancer Institute, 450 Brookline Avenue, Boston, Massachusetts 02215, USA [2] Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, Massachusetts 02115, USA.
9
1] Massachusetts General Hospital Cancer Center, Massachusetts General Hospital, 55 Fruit Street, Boston, Massachusetts 02114, USA [2] Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [3] Broad Institute of MIT and Harvard, Cancer Genome Comparative Analysis Group, 415 Main Street, Cambridge, Massachusetts 02142, USA.
10
1] Department of Medicine, Harvard Medical School, 25 Shattuck Street, Boston, Massachusetts 02115, USA [2] Broad Institute of MIT and Harvard, Cancer Genome Comparative Analysis Group, 415 Main Street, Cambridge, Massachusetts 02142, USA [3] Department of Pathology, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, Massachusetts 02114, USA.

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.

PMID:
25758528
PMCID:
PMC4357281
DOI:
10.1038/ncomms7377
[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Supplementary concept, Secondary source ID, Grant support

Publication types

MeSH terms

Substances

Supplementary concept

Secondary source ID

Grant support

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center