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.
BACKGROUND: Triple-negative breast cancers lack expression of estrogen and progesterone receptors and overexpression of humanepidermal 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-srcsarcoma 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: M Ahmadi; Z Ahmadihosseini; S J Allison; S Begum; K Rockley; M Sadiq; S Chintamaneni; R Lokwani; N Hughes; R M Phillips Journal: Br J Pharmacol Date: 2014-01 Impact factor: 8.739
Authors: Muralidharan Anbalagan; Mei Sheng; Brian Fleischer; Yifang Zhang; Yuanjun Gao; Van Hoang; Margarite Matossian; Hope E Burks; Matthew E Burow; Bridgette M Collins-Burow; David Hangauer; Brian G Rowan Journal: Mol Cancer Res Date: 2017-07-27 Impact factor: 5.852
Authors: Gang Lu; Qing Zhang; Ying Huang; Jiaxi Song; Ross Tomaino; Tobias Ehrenberger; Elgene Lim; Wenbin Liu; Roderick T Bronson; Michaela Bowden; Jane Brock; Ian E Krop; Deborah A Dillon; Steven P Gygi; Gordon B Mills; Andrea L Richardson; Sabina Signoretti; Michael B Yaffe; William G Kaelin Journal: Cancer Cell Date: 2014-08-11 Impact factor: 31.743