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The molecular mechanisms underlying the therapeutic resistance of cancer stem cells

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Abstract

Chemo-resistance and radio-resistance are a major cause of recurrence and progression of many cancers, regardless of improvements in therapies. Since cancer stem cells (CSCs) were identified as a rare population with the abilities of self-renewal; tumor initiation; aberrant differentiation, which contributes to tumor heterogeneity; and resistance to anticancer therapeutics, they have been considered a major cause of tumor recurrence post-therapy and a primary therapeutic target in relapse prevention. A number of studies have demonstrated the mechanisms underlying chemo-resistance and radio-resistance of CSCs. In this review, we describe intrinsic and extrinsic factors underlying CSC chemo-resistance and radio-resistance. The intrinsic factors regulate CSC signaling pathways involved in stem cell signaling, anti-apoptotic pathways, ABC transporter expression, and DNA damage repair systems. The extrinsic factors include the resistance mechanisms resulting from the interactions between CSCs and the microenvironment composed of vessels, fibroblasts, immune cells, extracellular matrix, and diverse soluble factors. Furthermore, we introduce diverse therapeutic agents used in experimental or clinical trials to target CSCs. Understanding how CSCs acquire resistance to anticancer therapeutics will give us opportunity to develop improved therapeutic approaches.

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Acknowledgments

This work was supported by the National Nuclear Technology Program through the National Research Foundation (NRF) of Korea funded by the Ministry of Science, ICT and Future Planning (No. 2013M2A2A7042530 to H. Kim). H.-Y. Jeon was supported by the Kwanjeong Educational Foundation Domestic Scholarship.

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  1. Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, 5-ga, Anam-dong, Seongbuk-gu, Life Science West Building 207, Seoul, 136-713, Republic of Korea

    Jun-Kyum Kim, Hee-Young Jeon & Hyunggee Kim

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  1. Jun-Kyum Kim
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Correspondence to Hyunggee Kim.

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Jun-Kyum Kim and Hee-Young Jeon have contributed equally to this work.

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Kim, JK., Jeon, HY. & Kim, H. The molecular mechanisms underlying the therapeutic resistance of cancer stem cells. Arch. Pharm. Res. 38, 389–401 (2015). https://doi.org/10.1007/s12272-014-0531-1

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