title: Src: a potential target for the treatment of triple-negative breast cancer.
abstract: BACKGROUND
  Triple-negative breast cancers lack expression of estrogen and progesterone receptors and overexpression of human epidermal growth factor receptor 2 (HER2). Unlike other subgroups of patients with breast cancer, targeted therapy is currently unavailable for these patients. The aim of this study was to investigate v-src sarcoma viral oncogene homolog (Src) as a potential target for the treatment of triple-negative breast cancer.
  
  
  METHODS
  Expression of Src was measured in 87 triple-negative and 93 non-triple-negative breast cancers. Dasatinib (an inhibitor of Src) was tested in a panel of breast cancer cell lines.
  
  
  RESULTS
  Cytoplasmic expression of Src was detected in 83 (95%) triple-negative samples versus 78 (84%) non-triple-negative samples (P = 0.012), while membrane Src was detected in 78% triple-negative compared with 38% of non-triple-negative specimens (P < 0.0001). Dasatinib inhibited growth in three of five triple-negative cell lines (IC(50) < 1 μM). Dasatinib combined with cisplatin was synergistic in the three dasatinib-sensitive cell lines (combination index < 0.9). Dasatinib, in combination with 5'-deoxy-5'-fluoruridine, displayed synergy or additivity. Moderate synergy was observed with docetaxel (Taxotere) in two cell lines but the combination was antagonistic in HCC-1143 cells.
  
  
  CONCLUSIONS
  We conclude that dasatinib with cisplatin is a rational drug combination for testing in triple-negative breast cancer.
authors.affiliation: Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
authors.forename: D
authors.initials: D
authors.lastname: Tryfonopoulos
authors.forename: S
authors.initials: S
authors.lastname: Walsh
authors.forename: D M
authors.initials: DM
authors.lastname: Collins
authors.forename: L
authors.initials: L
authors.lastname: Flanagan
authors.forename: C
authors.initials: C
authors.lastname: Quinn
authors.forename: B
authors.initials: B
authors.lastname: Corkery
authors.forename: E W
authors.initials: EW
authors.lastname: McDermott
authors.forename: D
authors.initials: D
authors.lastname: Evoy
authors.forename: A
authors.initials: A
authors.lastname: Pierce
authors.forename: N
authors.initials: N
authors.lastname: O'Donovan
authors.forename: J
authors.initials: J
authors.lastname: Crown
authors.forename: M J
authors.initials: MJ
authors.lastname: Duffy
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D003593:Cytoplasm / Q000201:enzymology; D000069439:Dasatinib; D005260:Female; D006801:Humans; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011743:Pyrimidines / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis; D013844:Thiazoles / Q000008:administration & dosage; D019061:src-Family Kinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D002945:Cisplatin; D000069439:Dasatinib; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013844:Thiazoles; D019061:src-Family Kinases