Abstract
Simple SummaryTriple negative breast cancer lacks targeted therapies and has poor prognosis; chemotherapy is currently the main treatment modality. Growing evidence has shown that breast cancer stem cells are associated with tumor initiation and metastasis and may play a critical role in chemoresistance. Multiple targets against breast cancer stem cells are now under investigation. Recent advances in the role of breast cancer stem cells in triple negative breast cancer and the identification of cancer stem cell biomarkers have paved the way for the development of new targeted therapies. The discovery of potential molecular signaling pathways targeting breast cancer stem cells to overcome chemoresistance and prevent metastasis will improve the overall survival of patients with triple negative breast cancer.Triple negative breast cancer (TNBC) remains an aggressive disease due to the lack of targeted therapies and low rate of response to chemotherapy that is currently the main treatment modality for TNBC. Breast cancer stem cells (BCSCs) are a small subpopulation of breast tumors and recognized as drivers of tumorigenesis. TNBC tumors are characterized as being enriched for BCSCs. Studies have demonstrated the role of BCSCs as the source of metastatic disease and chemoresistance in TNBC. Multiple targets against BCSCs are now under investigation, with the considerations of either selectively targeting BCSCs or co-targeting BCSCs and non-BCSCs (majority of tumor cells). This review article provides a comprehensive overview of recent advances in the role of BCSCs in TNBC and the identification of cancer stem cell biomarkers, paving the way for the development of new targeted therapies. The review also highlights the resultant discovery of cancer stem cell targets in TNBC and the ongoing clinical trials treating chemoresistant breast cancer. We aim to provide insights into better understanding the mutational landscape of BCSCs and exploring potential molecular signaling pathways targeting BCSCs to overcome chemoresistance and prevent metastasis in TNBC, ultimately to improve the overall survival of patients with this devastating disease.
Highlights
Studies have shown that CD44+/CD24− and ALDH1+ breast cancer stem cells are enriched in Triple negative breast cancer (TNBC) and may contribute to the propensity of TNBC for chemoresistance and tumor metastasis [16,17]
Breast cancer stem cells (BCSCs) are a small subpopulation of breast tumors that play a vital role in metastatic disease and drug resistance
TNBC tumors are characterized as being enriched for BCSCs
Summary
Studies have shown that CD44+/CD24− and ALDH1+ breast cancer stem cells are enriched in TNBC and may contribute to the propensity of TNBC for chemoresistance and tumor metastasis [16,17]. This tumor evasion mechanism from chemotherapy is likely to play a more important role in tumorigenesis and outcome in TNBC compared with non-TNBCs such as luminal A type breast cancer. Specific drugs to Notch, Sonic hedgehog (Shh) and Wnt signaling pathways of BCSCs are under investigation [20] Immunotherapies, such as monoclonal antibody against CD44, and gene-edit technology such as Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are other potential treatment options that target BCSCs [21]
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