Targeting drug resistant stem cells in a human epidermal growth factor receptor‑2‑enriched breast cancer model
Published online on: April 11, 2019
Copyright: © Telang et al.
This is an open access article distributed under the terms of Creative Commons Attribution License.
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Human epidermal growth factor receptor‑2 (HER‑2) expression in the presence or absence of hormone receptors dictates HER‑2‑targeted therapy with or without endocrine therapy. These treatment options lead to long‑term systemic toxicity, multi‑drug resistance and the emergence of therapy‑resistant cancer stem cells. These limitations emphasize the need for the development of reliable model systems with which to evaluate stem cell signaling molecules as testable targets for stem cell therapy, and to identify less toxic testable alternatives for therapeutic resistance. In this study, with the aim of identifying such a system, HER‑2‑positive tumorigenic 184‑B5/HER cells were used as a model of HER‑2‑enriched breast cancer. The epidermal growth factor receptor (EGFR)/HER‑2 specific small molecule inhibitor, lapatinib (LAP), was used to select the drug resistant phenotype. Vitamin A derivative, all trans‑retinoic acid (ATRA), and rosemary terpenoid carnosol (CSOL) represented the test agents. The LAP‑resistant (LAP‑R) phenotype exhibited an upregulated expression of select stem cell specific markers, including tumor spheroids, CD44, NANOG and Oct‑4. These data provide evidence for the effective development of a LAP‑R cancer stem cell model. ATRA and CSOL inhibited the expression of stem cell‑specific markers in the LAP‑R phenotype, suggesting that natural products may possess stem cell targeted therapeutic efficacy via the downregulation of select signaling molecules that are functional in cancer stem cells. On the whole, the findings of this study validate a cancer stem cell model which is able to identify natural products as testable alternatives for the treatment of therapy‑resistant HER‑2‑enriched breast cancer.