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Int. J. Mol. Sci. 2017, 18(5), 903; doi:10.3390/ijms18050903

188Re-Liposome Can Induce Mitochondrial Autophagy and Reverse Drug Resistance for Ovarian Cancer: From Bench Evidence to Preliminary Clinical Proof-of-Concept

1
School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
2
Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei 112, Taiwan
3
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan
4
Institute of Traditional Medicine, School of Medicine, National Yang-Ming University, Taipei 112, Taiwan
5
Department of Oncology, Taipei Veterans General Hospital, Taipei 112, Taiwan
6
Institute of Oral Biology, National Yang-Ming University, Taipei 112, Taiwan
7
Departments of Nuclear Medicine Radiology, Taipei Veterans General Hospital, Taipei 112, Taiwan
8
Biophotonics and Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan
9
Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan 325, Taiwan
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Academic Editor: Kwong-Kwok Wong
Received: 6 March 2017 / Revised: 17 April 2017 / Accepted: 20 April 2017 / Published: 25 April 2017
(This article belongs to the Special Issue Gynecologic Oncology: From Molecular Mechanisms to Targeted Therapies)
View Full-Text   |   Download PDF [4679 KB, uploaded 27 April 2017]   |  

Abstract

Despite standard treatment, about 70% of ovarian cancer will recur. Cancer stem cells (CSCs) have been implicated in the drug-resistance mechanism. Several drug resistance mechanisms have been proposed, and among these, autophagy plays a crucial role for the maintenance and tumorigenicity of CSCs. Compared to their differentiated counterparts, CSCs have been demonstrated to display a significantly higher level of autophagy flux. Moreover, mitophagy, a specific type of autophagy that selectively degrades excessive or damaged mitochondria, is shown to contribute to cancer progression and recurrence in several types of tumors. Nanomedicine has been shown to tackle the CSCs problem by overcoming drug resistance. In this work, we developed a nanomedicine, 188Re-liposome, which was demonstrated to target autophagy and mitophagy in the tumor microenvironment. Of note, the inhibition of autophagy and mitophagy could lead to significant tumor inhibition in two xenograft animal models. Lastly, we presented two cases of recurrent ovarian cancer, both in drug resistance status that received a level I dose from a phase I clinical trial. Both cases developing drug resistance showed drug sensitivity to 188Re-liposome. These results suggest that inhibition of autophagy and mitophagy by a nanomedicine may be a novel strategy to overcome drug resistance in ovarian cancer. View Full-Text
Keywords: ovarian cancer; cancer stem cells; autophagy; mitophagy ovarian cancer; cancer stem cells; autophagy; mitophagy
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Chang, C.-M.; Lan, K.-L.; Huang, W.-S.; Lee, Y.-J.; Lee, T.-W.; Chang, C.-H.; Chuang, C.-M. 188Re-Liposome Can Induce Mitochondrial Autophagy and Reverse Drug Resistance for Ovarian Cancer: From Bench Evidence to Preliminary Clinical Proof-of-Concept. Int. J. Mol. Sci. 2017, 18, 903.

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