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Updated: Jun 4, 2026
Studying Triple Negative Breast Cancer Using Orthotopic Breast Cancer Model
Published on: March 20, 2020
Src: a potential target for the treatment of triple-negative breast cancer
D Tryfonopoulos1, S Walsh, D M Collins
1Molecular Therapeutics for Cancer Ireland, National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
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.
Insights
Triple-negative breast cancer, lacking targeted therapies, shows high Src expression. The Src inhibitor dasatinib, particularly combined with cisplatin, demonstrates promising therapeutic potential in preclinical models.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Triple-negative breast cancer (TNBC) lacks targeted therapies due to absent estrogen/progesterone receptors and HER2 overexpression.
- v-src sarcoma viral oncogene homolog (Src) is investigated as a potential therapeutic target for TNBC.
- Current treatment options for TNBC are limited compared to other breast cancer subtypes.
Purpose of the Study:
- To evaluate Src as a potential therapeutic target in triple-negative breast cancer.
- To assess the efficacy of dasatinib, a Src inhibitor, in TNBC cell lines.
- To explore combination therapies involving dasatinib for TNBC treatment.
Main Methods:
- Src expression was quantified in 87 triple-negative and 93 non-triple-negative breast cancer samples.
- Dasatinib's effect on breast cancer cell line growth was evaluated.
- Synergistic effects of dasatinib combined with cisplatin, 5'-deoxy-5'-fluoruridine, and docetaxel were assessed.
Main Results:
- Significantly higher cytoplasmic (95% vs 84%) and membrane (78% vs 38%) Src expression in TNBC compared to non-TNBC.
- Dasatinib inhibited growth in 3 of 5 TNBC cell lines (IC(50) < 1 μM).
- Dasatinib plus cisplatin showed synergy in sensitive TNBC cell lines; additive or synergistic effects observed with 5'-deoxy-5'-fluoruridine; variable effects with docetaxel.
Conclusions:
- Src is highly expressed in triple-negative breast cancer, suggesting its role in TNBC pathogenesis.
- Dasatinib demonstrates preclinical efficacy against a subset of TNBC cell lines.
- The combination of dasatinib and cisplatin represents a rational therapeutic strategy for clinical investigation in TNBC.
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