Systematic name M16369
Brief description Genes whose expression negatively correlated with resistance of breast cancer cell lines to dasatinib [PubChem=3062316].
Full description or abstract Dasatinib is a multitargeted kinase inhibitor that was recently approved for the treatment of chronic myelogenous leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia with resistance or intolerance to prior therapy. It is also in clinical trials for treating patients with solid tumors. The identification of molecular markers predictive of response to dasatinib could assist in clinical development by selecting patients most likely to derive clinical benefit. Using baseline gene expression profiling of a panel of 23 breast cancer cell lines, we identified genomic signatures highly correlated with in vitro sensitivity to dasatinib. The ability of these signatures to predict dasatinib sensitivity was further confirmed and validated in independent test cell lines. A six-gene model was used to correctly predict dasatinib sensitivity in 11 out of 12 (92%) additional breast and 19 out of 23 (83%) lung cancer cell lines. Quantitative real-time PCR and immunohistochemical assays further confirmed the differential expression pattern of selected markers. Finally, these gene signatures were observed in a subset of primary breast, lung, and ovarian tumors suggesting potential utility in patient selection. The subset of breast cancer patients expressing the dasatinib-sensitive signature includes a distinct clinical and molecular subgroup: the so-called triple negative (i.e., estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) or basal breast cancer subtype. This patient population has a poor prognosis and currently has few effective treatment options. Our results implicate that dasatinib may represent a valuable treatment option in this difficult-to-treat population. To test this hypothesis, clinical studies are now under way to determine the activity of dasatinib in these patients.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 17332353   Authors: Huang F,Reeves K,Han X,Fairchild C,Platero S,Wong TW,Lee F,Shaw P,Clark E
Exact source Table 2: S2N score < 0
Related gene sets (show 1 additional gene sets from the source publication)

(show 2 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform or
identifier namespace
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 70 genes
Gene families ? Categorize these 70 genes by gene family
Show members (show 71 source identifiers mapped to 70 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.