Ovarian cancer stem cell: A potential therapeutic target for overcoming multidrug resistance

Mihanfar, Aynaz; Attari, Javad Aghazadeh; Mohebbi, Iraj; Majidinia, Maryam; Kaviani, Mojtaba; Yousefi, Mehdi; Yousefi, Bahman

doi:10.1002/jcp.26768

Cited by 50 publications

(40 citation statements)

References 155 publications

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“…Ovarian cancer is an umbrella term for a broad range of neoplasms of different histopathological types, including serous, endometrioid, clear cell, and mucinous; importantly, these subtypes exhibit different responses to drug treatment [89]. The proportion of CSCs in ovarian cancer varies between 0.1% and 30% depending on the disease type and stage [90].…”

Section: Csc-targeting Therapiesmentioning

confidence: 99%

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

Shibata

Hoque

2019

Cancers

158

108

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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.

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Section: Csc-targeting Therapiesmentioning

confidence: 99%

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

Shibata

Hoque

2019

Cancers

158

108

View full text Add to dashboard Cite

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“…Despite substantial improvements in treatment of ovarian cancer in the past several decades, the prognosis of ovarian cancer patients is still dismal, which is largely attributed to chemotherapeutic resistance after a long period of treatment. Cancer stem cells (CSCs) that are a minority population of cells with the abilities of unrestrained proliferation and self-renewal have been identified to contribute to the failure of chemotherapy in ovarian cancer patients 2, 3. Several lines of evidence have reported that CSCs are crucial mediators in the induction and maintenance of chemotherapeutic resistance in several human cancers,4, 5 including ovarian cancer 6, 7.…”

Section: Introductionmentioning

confidence: 99%

Silencing LGR6 Attenuates Stemness and Chemoresistance via Inhibiting Wnt/β-Catenin Signaling in Ovarian Cancer

Ruan

Liu

Zhong

et al. 2019

Molecular Therapy - Oncolytics

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Leucine-rich-repeat-containing G protein-coupled receptors (LGRs) have been widely found to be implicated with development and progression in multiple cancer types. However, the clinical significance and biological functions of LGR6 in ovarian cancer remains unclear. In this study, LGR6 expression was mainly examined by immunohistochemistry. Functional assays in vitro and animal experiments in vivo were carried out to explore the effect of LGR6 on cancer stem cell (CSC) characteristics and chemotherapeutic responses in ovarian cancer cells. Luciferase assays and GSEA were used to discern the underlying mechanisms contributing to the roles of LGR6 in ovarian cancer. Here, we reported that LGR6 was upregulated in ovarian cancer, which positively correlated with poor chemotherapeutic response and progression survival in ovarian cancer patients. Loss-of-function assays showed that downregulating LGR6 abrogated the CSC-like phenotype and chemoresistance in vitro. More importantly, silencing LGR6 improved the chemoresistance of ovarian cancer cells to cisplatin in vivo. Mechanistic investigation further revealed that silencing LGR6 inhibited stemness and chemoresistance by repressing Wnt/b-catenin signaling. Collectively, our results uncover a novel mechanism contributing to LGR6-induced chemotherapeutic resistance in ovarian cancer, providing the evidence for LGR6 as a potential therapeutic target in ovarian cancer.

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“…Çoklu ilaç direnci (ÇİD) kemoterapinin etkisini azaltan en büyük sorunlardan biridir ve hücre içi ilaç alıkonmasının düşük olması, hücre dışına ilaç akışının artması, detoksifikasyon sistemlerinin aktivitesi, gelişmiş DNA onarım mekanizmaları ve kusurlu apoptoz gibi nedenlerle ortaya çıkmaktadır. Kanser hücrelerindeki çoklu ilaç direncinin kemoterapi ilaçlarını hücreden dışarı pompalayıp hücre içi ilaç konsantrasyonunu azaltan P-glikoproteinlerin (P-gp) aşırı ekspresyonu ile ilişkili olduğu gösterilmiştir [1][2][3][4][5]. İlacın serum dozunun artırılması çoklu ilaç direncine bir çözüm olsa da aynı zamanda normal dokular üzerinde de toksik etkilerin açığa çıkması kaçınılmazdır.…”

Section: Gi̇ri̇ş (Introduction)unclassified

Potansiyel doksorubisin taşıyıcı sistemi olarak PEG-endozom parçalayıcı peptit konjugatının değerlendirilmesi

Şen

Top

2020

Gazi Üniversitesi Mühendislik Mimarlık Fakültesi Dergisi

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Solid phase peptide and PEG conjugation with high efficiency  Preparation of pH sensitive drug delivery systems  Formation of selfassembled nanostructures Figure A. DOX release curves of the mPEG-oxime-DOX and mPEG-peptide-oxime-DOX obtained at pH 7.4 and pH 5.0 Purpose: In this study, it was aimed to assess the physicochemical and doxorubicin (DOX) release properties of a PEGylated TAT-derived peptide carrier system as a preliminary investigation. Theory and Methods: TAT-derived peptide with a sequence of G2RQR3QR3G2S was synthesized using Fmoc strategy in solid state. mPEG-COOH (Mn = 1900 Da) was conjugated to N-terminus of the peptide on the resin. DOX was conjugated to the mPEG-peptide conjugate via acid labile oxime bond. DOX-release, self-assembly, and stability properties of the resultant drug delivery system (DDS) denoted as mPEG-peptide-oxime-DOX were evaluated at pH 5.0 and pH 7.4 and compared with those of the control DDS lack of peptide sequence, mPEG-oxime-DOX. Drug release profiles of the DDSs were obtained using dialysis method. Size distribution and stability of the DDSs were determined via dynamic light scattering. Results: MALDI-TOF-MS analysis results indicated that both the peptide and the conjugate were synthesized successfully. For mPEG-oxime-DOX, pH dependent DOX release was obtained confirming pH responsive property of oxime bond. mPEG-peptide-oxime-DOX seemed to exhibit quite low DOX release (~10-15 %) for both pH, which suggested possible interactions between DOX and the peptide preventing DOX to pass through dialysis membrane. Initial median size (D50) value of the mPEG-oxime-DOX was measured as ~24 nm independent of pH. For mPEG-peptide-oxime-DOX, D50 values were obtained as ~3 nm and ~6 nm at pH 5.0 and pH 7.4, respectively and indicated its pH controlled aggregation behavior. Sizes of both DDSs, tended to increase upon incubation at physiological conditions for 1 day. Conclusion: Comparison of the stability behavior of the similar mPEG-DOX and mPEG-peptide-DOX conjugates developed in our group indicated that longer PEG chains should be used to enhance the stability of these kinds of DDSs.

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Ovarian cancer stem cell: A potential therapeutic target for overcoming multidrug resistance

Cited by 50 publications

References 155 publications

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

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

Silencing LGR6 Attenuates Stemness and Chemoresistance via Inhibiting Wnt/β-Catenin Signaling in Ovarian Cancer

Potansiyel doksorubisin taşıyıcı sistemi olarak PEG-endozom parçalayıcı peptit konjugatının değerlendirilmesi

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