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Targeting Cancer Stem Cells: A Strategy for Effective Eradication of Cancer

1
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD 21231 USA
2
Department of Breast and Endocrine Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya 4668550, Japan
3
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
4
Department of Urology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
*
Author to whom correspondence should be addressed.
Cancers 2019, 11(5), 732; https://doi.org/10.3390/cancers11050732
Received: 11 April 2019 / Revised: 19 May 2019 / Accepted: 23 May 2019 / Published: 27 May 2019
(This article belongs to the Special Issue Advances in Cancer Stem Cell Research)
Cancer stem cells (CSCs) are subpopulations of tumor cells with the ability to self-renew, differentiate, and initiate and maintain tumor growth, and they are considered to be the main drivers of intra- and inter-tumoral heterogeneity. While conventional chemotherapy can eradicate the majority of non-CSC tumor cells, CSCs are often drug-resistant, leading to tumor recurrence and metastasis. The heterogeneity of CSCs is the main challenge in developing CSC-targeting therapy; therefore, we and other investigators have focused on developing novel therapeutic strategies that combine conventional chemotherapy with inhibitors of CSC-regulating pathways. Encouraging preclinical findings have suggested that CSC pathway blockade can indeed enhance cellular sensitivity to non-targeted conventional therapy, and this work has led to several ongoing clinical trials of CSC pathway inhibitors. Our studies in bladder cancer and lung adenocarcinoma have demonstrated a crucial role of YAP1, a transcriptional regulator of genes that promote cell survival and proliferation, in regulating CSC phenotypes. Moreover, using cell lines and patient-derived xenograft models, we showed that inhibition of YAP1 enhances the efficacy of conventional therapies by attenuating CSC stemness features. In this review, we summarize the therapeutic strategies for targeting CSCs in several cancers and discuss the potential and challenges of the approach. View Full-Text
Keywords: cancer; cancer stem cell; YAP1; verteporfin; combinational therapy cancer; cancer stem cell; YAP1; verteporfin; combinational therapy
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Shibata, M.; Hoque, M.O. Targeting Cancer Stem Cells: A Strategy for Effective Eradication of Cancer. Cancers 2019, 11, 732.

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