Dasatinib Sensitizes Triple Negative Breast Cancer Cells To Chemotherapy By Targeting Breast Cancer Stem Cells | 91101
Journal of Biotechnology & Biomaterials
Like us on:
Our Group organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.
Patients with triple negative breast cancer (TNBC) exhibit poor prognosis and are at high risk of tumor relapse and metastasis
due to the resistance to conventional chemotherapy treatments. Tumor recurrence and resistance to chemotherapy have
been in part attributed to the presence of breast cancer stem cells (BCSCs), a subpopulation of breast cancer cells that possesses
stem-like properties. Therefore, targeting BCSCs is a priority to overcoming chemotherapy failure in TNBCs. We generated
chemotherapy-resistant TNBC cells through cyclic treatments with paclitaxel (pac). The pac-resistant cells displayed increased
self-renewal potential and higher percentage of BCSC subpopulations compared to the parental TNBC cells. A screen with
various kinase inhibitors revealed dasatinib, a Src kinase family inhibitor, as a potent suppressor of BCSC numbers and a
blocker of self-renewal ability in chemotherapy-resistant breast cancer cells. We also found dasatinib to block pac-induced
BCSC enrichment and Src activation in both parental and pac-resistant TNBC cells. Interestingly, dasatinib induced an
epithelial differentiation of the pac-resistant mesenchymal cells, further resulting in their enhanced sensitivity to paclitaxel.
The combination treatment of dasatinib and paclitaxel not only decreased the proportion of BCSCs and their self-renewal
capacity but also synergistically reduced cell viability of pac-resistant cells. In vivo studies, using xenograft mouse preclinical
models of breast cancer further demonstrated the efficiency of the dasatinib/paclitaxel combination treatment in inhibiting
tumor growth. Together, these results highlight dasatinib as a promising anti-BCSC drug that could be used in combination
with paclitaxel to overcome chemotherapy resistance in TNBC.
Jun Tian is currently a fifth year PhD student in Department of Medicine, McGill University, Canada. She has received her Bachelor of Science degree from Nankai University, China in 2013. Her research interest focuses on studying the role of breast cancer stem cells in breast cancer initiation, metastasis and chemotherapy resistance. So far, she has published seven co-authored scientific articles in peer-reviewed journals.