Systematic identification of genomic markers of drug sensitivity in cancer cells.
Nature
; 483(7391): 570-5, 2012 Mar 28.
Article
in En
| MEDLINE
| ID: mdl-22460902
ABSTRACT
Clinical responses to anticancer therapies are often restricted to a subset of patients. In some cases, mutated cancer genes are potent biomarkers for responses to targeted agents. Here, to uncover new biomarkers of sensitivity and resistance to cancer therapeutics, we screened a panel of several hundred cancer cell lines--which represent much of the tissue-type and genetic diversity of human cancers--with 130 drugs under clinical and preclinical investigation. In aggregate, we found that mutated cancer genes were associated with cellular response to most currently available cancer drugs. Classic oncogene addiction paradigms were modified by additional tissue-specific or expression biomarkers, and some frequently mutated genes were associated with sensitivity to a broad range of therapeutic agents. Unexpected relationships were revealed, including the marked sensitivity of Ewing's sarcoma cells harbouring the EWS (also known as EWSR1)-FLI1 gene translocation to poly(ADP-ribose) polymerase (PARP) inhibitors. By linking drug activity to the functional complexity of cancer genomes, systematic pharmacogenomic profiling in cancer cell lines provides a powerful biomarker discovery platform to guide rational cancer therapeutic strategies.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Screening Assays, Antitumor
/
Genetic Markers
/
Genome, Human
/
Drug Resistance, Neoplasm
/
Genes, Neoplasm
/
Neoplasms
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
Nature
Year:
2012
Document type:
Article
Affiliation country:
United kingdom