Cholangiocarcinoma therapy with nanoparticles that combine downregulation of MicroRNA-210 with inhibition of cancer cell invasiveness

Xie, Ying; Wang, Yazhe; Li, Jing; H, Yu; Jaramillo, Lee; Wehrkamp, Cody J.; Phillippi, Mary Anne; Mohr, Ashley M.; Chen, Yi; Talmon, Geoffrey A.; Mott, Justin L.; Oupický, David

doi:10.7150/thno.26506

Cited by 34 publications

(20 citation statements)

References 67 publications

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“…In particular, the domain of combination therapy should be pursued to develop a combination of targeted therapy and immunotherapy [196]. Xie et al [192] developed a novel therapy combining nanotherapeutic blockade of CXCR4 by polymeric CXCR4 antagonist (PCX) with inhibition of hypoxia-inducible miR-210. In their study, combination PCX/anti-miR-210 nanoparticles resulted in significant CCA cell death through induction of apoptosis and reduced the number of cancer stem-like cells.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

“…Furthermore, the nanoparticles sensitized CCA cells to standard gemcitabine and cisplatin combination treatment by reversing hypoxia-induced drug resistance. The nanoparticles showed enhanced in vivo antitumor activity in a CCA xenograft model [192]. Therefore, combination PCX/anti-miR-210 nanoparticle + gemcitabine/cisplatin might be a promising combination therapy for CCA.…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

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Role of Cancer Stem Cells in Cholangiocarcinoma and Therapeutic Implications

Chu

2019

IJMS

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Cholangiocarcinoma (CCA) is the second most common type of liver cancer, and is highly aggressive with very poor prognosis. CCA is classified into intrahepatic cholangiocarcinoma (iCCA) and extra-hepatic cholangiocarcinoma (eCCA), which is further stratified into perihilar (pCCA) and distal (dCCA). Cancer stem cells (CSCs) are a subpopulation of cancer cells capable of tumor initiation and malignant growth, and are also responsible for chemoresistance. Thus, CSCs play an important role in CCA carcinogenesis. Surface markers such as CD133, CD24, CD44, EpCAM, Sox2, CD49f, and CD117 are important for identifying and isolating CCA CSCs. CSCs are present in the tumor microenvironment (TME), termed ‘CSC niche’, where cellular components and soluble factors interact to promote tumor initiation. Epithelial-to-mesenchymal transition (EMT) is another important mechanism underlying carcinogenesis, involved in the invasiveness, metastasis and chemoresistance of cancer. It has been demonstrated that EMT plays a critical role in generating CSCs. Therapies targeting the surface markers and signaling pathways of CCA CSCs, proteins involved in TME, and immune checkpoint proteins are currently under investigation. Therefore, this review focuses on recent studies on the roles of CSCs in CCA; the possible therapeutic strategies targeting CSCs of CCA are also discussed.

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Section: Therapeutic Implicationsmentioning

confidence: 99%

Section: Therapeutic Implicationsmentioning

confidence: 99%

Role of Cancer Stem Cells in Cholangiocarcinoma and Therapeutic Implications

Chu

2019

IJMS

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“…The study by Li et al contributed to the current knowledge of intercellular communications between CCA and microenvironment, suggesting a potential therapeutic role of miR-195 mimics in CCA. Xie et al developed cholesterol-modified polymeric C-X-C receptor type 4 (CXCR4) antagonist (PCX) nanoparticles, with codelivery of anti-miR-210 to cooperatively exert antitumor activity in CCA [ 137 ]. Inhibition of CXCR4 signaling decreases CCA cells migration and invasion [ 138 , 139 ].…”

Section: Mirnas As Therapeutic Targets In Cholangiocarcinomamentioning

confidence: 99%

“…The antitumor effect was also demonstrated in a CCA xenograft model. The results showed that an innovative nanotherapeutic approach that combined inhibition of CXCR4 and miR-210 could efficiently kill CCA cells through the induction of apoptosis [ 137 ].…”

Section: Mirnas As Therapeutic Targets In Cholangiocarcinomamentioning

confidence: 99%

The Emerging Role of MicroRNAs in Regulating the Drug Response of Cholangiocarcinoma

Huang

Yeh

2020

Biomolecules

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Cholangiocarcinoma (CCA) is the most common biliary malignancy, and has a poor prognosis. The median overall survival with the standard-of-care chemotherapy (Gemcitabine and cisplatin) in patients with advanced-stage CCA is less than one year. The limited efficacy of chemotherapy or targeted therapy remains a major obstacle to improving survival. The mechanisms involved in drug resistance are complex. Research efforts focusing on the distinct molecular mechanisms underlying drug resistance should prompt the development of treatment strategies that overcome chemoresistance or targeted drug resistance. MicroRNAs (miRNAs) are a class of evolutionarily conserved, short noncoding RNAs regulating gene expression at the post-transcriptional level. Dysregulated miRNAs have been shown to participate in almost all CCA hallmarks, including cell proliferation, migration and invasion, apoptosis, and the epithelial-to-mesenchymal transition. Emerging evidence demonstrates that miRNAs play a role in regulating responses to chemotherapy and targeted therapy. Herein, we present an overview of the current knowledge on the miRNA-mediated regulatory mechanisms underlying drug resistance among CCA. We also discuss the application of miRNA-based therapeutics to CCA, providing the basis for innovative treatment approaches.

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“…Xie et al . showed that targeting miR-210, in combination with polymeric CXCR4 antagonist (PCX), showed cytotoxic activity towards CCA cells and cancer stem-like cells (6). Epigenetic regulation of disease has seen an increase of focus since the discovery of non-coding RNAs.…”

Section: Epigenetics and Post-transcriptional Modificationmentioning

confidence: 99%