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The molecular landscape of colorectal cancer cell lines unveils clinically actionable kinase targets
- 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 :
- Drug
Colorectal cancer
media_common.quotation_subject
EGFR
colorectal cancer
cetuximab
Tyrosine kinase inhibition
General Physics and Astronomy
Bioinformatics
General Biochemistry, Genetics and Molecular Biology
03 medical and health sciences
Genetic Heterogeneity
0302 clinical medicine
Cell Line, Tumor
medicine
Humans
Anaplastic Lymphoma Kinase
Molecular Targeted Therapy
Receptor, Fibroblast Growth Factor, Type 2
030304 developmental biology
media_common
0303 health sciences
Multidisciplinary
Cetuximab
business.industry
Kinase
Proto-Oncogene Proteins c-ret
Receptor Protein-Tyrosine Kinases
General Chemistry
Genes, erbB-1
medicine.disease
3. Good health
ErbB Receptors
Cell culture
Precision oncology
030220 oncology & carcinogenesis
Cancer research
business
Colorectal Neoplasms
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....17e8f0dc0c3974d74bec96fab0dae712