Type

Journal Article

Authors

M J Duffy
J Crown
N O'Donovan
A Pierce
D Evoy
E W McDermott
B Corkery
C Quinn
L Flanagan
D M Collins
and 2 others

Subjects

Pharmacology

Topics
therapeutic use molecular targeted therapy humans metabolism thiazoles src family kinases female drug therapy cell line tumor enzymology protein kinase inhibitors antineoplastic combined chemotherapy protocols biosynthesis receptors estrogen administration dosage middle aged tumor markers biological pyrimidines cisplatin antagonists inhibitors breast neoplasms receptor erbb 2 receptors progesterone dasatinib cytoplasm

Src: a potential target for the treatment of triple-negative breast cancer. (2011)

Abstract 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. 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. 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. We conclude that dasatinib with cisplatin is a rational drug combination for testing in triple-negative breast cancer.
Collections Ireland -> Dublin City University -> PubMed

Full list of authors on original publication

M J Duffy, J Crown, N O'Donovan, A Pierce, D Evoy, E W McDermott, B Corkery, C Quinn, L Flanagan, D M Collins and 2 others

Experts in our system

1
Michael J Duffy
University College Dublin
 
2
John Crown
Dublin City University
Total Publications: 104
 
3
Norma O'Donovan
Dublin City University
Total Publications: 59
 
4
E W McDermott
University College Dublin
Total Publications: 49
 
5
B Corkery
Dublin City University
Total Publications: 5
 
6
C M Quinn
University College Dublin
Total Publications: 11
 
7
Denis M Collins
Dublin City University
Total Publications: 26