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The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets.
- Source :
-
Nature communications [Nat Commun] 2015 Apr 30; Vol. 6, pp. 7002. Date of Electronic Publication: 2015 Apr 30. - Publication Year :
- 2015
-
Abstract
- The development of molecularly targeted anticancer agents relies on large panels of tumour-specific preclinical models closely recapitulating the molecular heterogeneity observed in patients. Here we describe the mutational and gene expression analyses of 151 colorectal cancer (CRC) cell lines. We find that the whole spectrum of CRC molecular and transcriptional subtypes, previously defined in patients, is represented in this cell line compendium. Transcriptional outlier analysis identifies RAS/BRAF wild-type cells, resistant to EGFR blockade, functionally and pharmacologically addicted to kinase genes including ALK, FGFR2, NTRK1/2 and RET. The same genes are present as expression outliers in CRC patient samples. Genomic rearrangements (translocations) involving the ALK and NTRK1 genes are associated with the overexpression of the corresponding proteins in CRC specimens. The approach described here can be used to pinpoint CRCs with exquisite dependencies to individual kinases for which clinically approved drugs are already available.
- Subjects :
- Anaplastic Lymphoma Kinase
Cell Line, Tumor
Cetuximab
Colorectal Neoplasms genetics
Genes, erbB-1
Genetic Heterogeneity
Humans
Molecular Targeted Therapy
Proto-Oncogene Proteins c-ret metabolism
Receptor Protein-Tyrosine Kinases genetics
Receptor, Fibroblast Growth Factor, Type 2 metabolism
Colorectal Neoplasms enzymology
ErbB Receptors antagonists & inhibitors
Receptor Protein-Tyrosine Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2041-1723
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Nature communications
- Publication Type :
- Academic Journal
- Accession number :
- 25926053
- Full Text :
- https://doi.org/10.1038/ncomms8002