Targeting Breast Cancer Stem Cells to Overcome Treatment Resistance

Despite advances in breast cancer diagnosis and treatment, many patients still fail therapy, resulting in disease progression, recurrence, and reduced overall survival. Historically, much focus has been put on the intrinsic subtyping based in the presence (or absence) of classical immunohistochemist...

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Bibliographic Details
Published in:	Molecules (Basel, Switzerland) Switzerland), 2018-08, Vol.23 (9), p.2193
Main Authors:	Palomeras, Sònia, Ruiz-Martínez, Santiago, Puig, Teresa
Format:	Article
Language:	eng
Subjects:	Animals Antigens Antineoplastic Agents - pharmacology Antineoplastic Agents - therapeutic use BCSCs BCSCs markers Biomarkers, Tumor Breast cancer Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - metabolism Breast Neoplasms - pathology Cancer therapies Cell adhesion & migration Cell division Cell Line, Tumor Cell Proliferation - drug effects Clinical Trials as Topic Drug resistance Drug Resistance, Neoplasm - genetics Female Gene expression Growth factors Humans Hypotheses Janus kinase Kinases Mesenchyme Molecular Targeted Therapy Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Population Protein-tyrosine kinase Protein-tyrosine kinase receptors resistance Review Signal Transduction - drug effects Stem cells targeted therapy Transcription Transcription factors Treatment Outcome Tumor necrosis factor-α Tumors Tyrosine
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Summary:	Despite advances in breast cancer diagnosis and treatment, many patients still fail therapy, resulting in disease progression, recurrence, and reduced overall survival. Historically, much focus has been put on the intrinsic subtyping based in the presence (or absence) of classical immunohistochemistry (IHC) markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-related protein (HER2). However, it is widely understood that tumors are composed of heterogeneous populations of cells with a hierarchical organization driven by cancer stem cells (CSCs). In breast tumors, this small population of cells displaying stem cell properties is known as breast CSCs (BCSCs). This rare population exhibit a CD44⁺/CD24 phenotype with high ALDH activity (ALDH⁺), and possesses higher tolerability to chemotherapy, hormone therapy, and radiotherapy and is able to reproduce the bulk of the tumor after reduction of cell populations sensitive to first-line therapy leading to disease relapse. In this review, we present special attention to BCSCs with future directions in the establishment of a therapy targeting this population. Drugs targeting the main BCSCs signaling pathways undergoing clinical trials are also summarized.
ISSN:	1420-3049 1420-3049