Effects of Cancer Stem Cells in Triple-Negative Breast Cancer and Brain Metastasis: Challenges and Solutions
Division of Neurosurgery, Department of Surgery, Taipei Medical University-Shuang Ho Hospital, New Taipei City 23561, Taiwan
Taipei Neuroscience Institute, Taipei Medical University, Taipei 11031, Taiwan
Taipei Medical University (TMU) Research Center for Cell Therapy and Regeneration Medicine, Taipei Medical University, Taipei 11031, Taiwan
Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2020, 12(8), 2122; https://doi.org/10.3390/cancers12082122
Received: 30 June 2020 / Revised: 25 July 2020 / Accepted: 27 July 2020 / Published: 31 July 2020
(This article belongs to the Special Issue Triple-Negative Breast Cancer: Molecular Characteristics, Treatment Challenges and Solutions)
A higher propensity of developing brain metastasis exists in triple-negative breast cancer (TNBC). Upon comparing the metastatic patterns of all breast cancer subtypes, patients with TNBC exhibited increased risks of the brain being the initial metastatic site, early brain metastasis development, and shortest brain metastasis-related survival. Notably, the development of brain metastasis differs from that at other sites owing to the brain-unique microvasculature (blood brain barrier (BBB)) and intracerebral microenvironment. Studies of brain metastases from TNBC have revealed the poorest treatment response, mostly because of the relatively backward strategies to target vast disease heterogeneity and poor brain efficacy. Moreover, TNBC is highly associated with the existence of cancer stem cells (CSCs), which contribute to circulating cancer cell survival before BBB extravasation, evasion from immune surveillance, and plasticity in adaptation to the brain-specific microenvironment. We summarized recent literature regarding molecules and pathways and reviewed the effects of CSC biology during the formation of brain metastasis in TNBC. Along with the concept of individualized cancer therapy, certain strategies, namely the patient-derived xenograft model to overcome the lack of treatment-relevant TNBC classification and techniques in BBB disruption to enhance brain efficacy has been proposed in the hope of achieving treatment success.