Src: a potential target for the treatment of triple-negative breast cancer

Ann Oncol. 2011 Oct;22(10):2234-40. doi: 10.1093/annonc/mdq757. Epub 2011 Feb 28.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / biosynthesis
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / enzymology*
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cisplatin / administration & dosage
  • Cytoplasm / enzymology
  • Dasatinib
  • Female
  • Humans
  • Middle Aged
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / administration & dosage
  • Pyrimidines / administration & dosage
  • Receptor, ErbB-2 / biosynthesis
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Thiazoles / administration & dosage
  • src-Family Kinases / antagonists & inhibitors*
  • src-Family Kinases / biosynthesis


  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Thiazoles
  • Receptor, ErbB-2
  • src-Family Kinases
  • Cisplatin
  • Dasatinib