Transformation from non-small-cell lung cancer to small-cell lung cancer: molecular drivers and cells of origin.

Lancet Oncol 2015 Apr;16(4):e165-72

Massachusetts General Hospital Cancer Center, Department of Medicine and Harvard Medical School, Boston, MA 02114, USA. Electronic address:

Lung cancer is the most common cause of cancer deaths worldwide. The two broad histological subtypes of lung cancer are small-cell lung cancer (SCLC), which is the cause of 15% of cases, and non-small-cell lung cancer (NSCLC), which accounts for 85% of cases and includes adenocarcinoma, squamous-cell carcinoma, and large-cell carcinoma. Although NSCLC and SCLC are commonly thought to be different diseases owing to their distinct biology and genomic abnormalities, the idea that these malignant disorders might share common cells of origin has been gaining support. This idea has been supported by the unexpected findings that a subset of NSCLCs with mutated EGFR return as SCLC when resistance to EGFR tyrosine kinase inhibitors develops. Additionally, other case reports have described the coexistence of NSCLC and SCLC, further challenging the commonly accepted view of their distinct lineages. Here, we summarise the published clinical observations and biology underlying tumours with combined SCLC and NSCLC histology and cancers that transform from adenocarcinoma to SCLC. We also discuss pre-clinical studies pointing to common potential cells of origin, and speculate how the distinct paths of differentiation are determined by the genomics of each disease.

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1470-2045(14)71180-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470698PMC
April 2015
23 Reads

Publication Analysis

Top Keywords

lung cancer
24
cells origin
12
small-cell lung
8
nsclc sclc
8
cancer small-cell
8
non-small-cell lung
8
cancer
7
lung
6
sclc
6
unexpected findings
4
sclc discuss
4
supported unexpected
4
idea supported
4
transform adenocarcinoma
4
adenocarcinoma sclc
4
subset nsclcs
4
mutated egfr
4
histology cancers
4
nsclcs mutated
4
support idea
4

Similar Publications