Cancer Stem Cells and Drug Resistance: The Potential of Nanomedicine

Vinogradov, Serguei V.; Wei, Xin

doi:10.2217/nnm.12.22

Cited by 422 publications

(334 citation statements)

References 68 publications

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“…We also observed that two primary ovarian cancers that expressed ROR1 were better able to grow as xenografts in immune-deficient mice than one that lacked expression of ROR1. Furthermore, within any one tumor population, the cells that expressed ALDH1, a marker of ovarian CSCs, expressed higher levels of ROR1, as did ovarian cancer cells that formed tumor spheroids, a functional characteristic associated with CSCs and EMT (43). Finally, we found that ROR1 + cells were better able to form spheroids, invade ECM, or engraft immunedeficient mice than ROR1 Neg cells from the same tumor population.…”

Section: Discussionmentioning

confidence: 65%

“…Compared with ROR1 Low cases, ROR1 Hi ovarian cancers had higher expression of gene signatures associated with the side population, which may contain CSCs (42). Moreover, ROR1 Hi ovarian cancers were enriched for expression of genes associated with embryonic stem cells and EMT (17,25), which facilitates the capacity of tumor cells to migrate and seed metastatic sites (21,43). We also observed that two primary ovarian cancers that expressed ROR1 were better able to grow as xenografts in immune-deficient mice than one that lacked expression of ROR1.…”

Section: Discussionmentioning

confidence: 99%

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Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Zhang

Cui

Lai

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

166

156

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Although initially responsive to chemotherapy, many patients with ovarian cancer subsequently develop relapsed and potentially fatal metastatic disease, which is thought to develop from cancer stem cells (CSCs) that are relatively resistant to conventional therapy. Here, we show that CSCs express a type I receptor tyrosine kinase-like orphan receptor (ROR1), which is expressed during embryogenesis and by many different cancers, but not normal postpartum tissues. Ovarian cancers with high levels of ROR1 had stem cell-like gene-expression signatures. Furthermore, patients with ovarian cancers with high levels of ROR1 had higher rates of relapse and a shorter median survival than patients with ovarian cancers that expressed low-to-negligible amounts of ROR1. We found that ROR1-positive (ROR1 + ) cells isolated from primary tumor-derived xenografts (PDXs) also expressed aldehyde dehydrogenase 1 (ALDH1) and had a greater capacity to form spheroids and to engraft immune-deficient mice than did ROR1-negative (ROR1 Neg ) ovarian cancer cells isolated from the same tumor population. Treatment with UC-961, an anti-ROR1 mAb, or shRNA silencing of ROR1 inhibited expression of the polycomb ring-finger oncogene, Bmi-1, and other genes associated with the epithelial-mesenchymal transition. Moreover, shRNA silencing of ROR1, depletion of ROR1 + cells, or treatment with UC-961 impaired the capacity of ovarian cancer cells to form spheroids or tumor xenografts. More importantly, treatment with anti-ROR1 affected the capacity of the xenograft to reseed a virgin mouse, indicating that targeting ROR1 may affect CSC self-renewal. Collectively, these studies indicate that ovarian CSCs express ROR1, which contributes to their capacity to form tumors, making ROR1 a potential target for the therapy of patients with ovarian cancer.ROR1 | ovarian cancer stem cell | monoclonal antibody | PDX mice model

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Zhang

Cui

Lai

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

166

156

View full text Add to dashboard Cite

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“…Our in vitro and in vivo data showed that CD133 + subpopulation exhibits EMT, metastasis and angiogenesis in melanoma. Previous studies showed that acquisition of chemoresistant is associated with high expression of multidrug resistant (MDR) protein, IL-8 and VEGF [3,8,9]. Our data indicates that CD133 + subpopulation exhibits higher percentage of SP phenotypes which probably associated with chemoresistance against DTIC, Dox, Dabrafenib and Trametinib [7].…”

Section: Commentarymentioning

confidence: 51%

Notch1-MAPK Signaling Axis is Essential in CD133+ Melanoma Initiating Cells

Kumar¹,

Pandey²,

Kundu³

2017

J Cell Signal

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“…NSCLC and other cancers contain a small population of Cancer Stem Cells (CSCs) which are resistant to radio-and chemotherapy and are responsible for cancer recurrence [19][20]. Therefore the discovery of a CSC-targeting drug would significantly improve chemotherapy outcomes for NSCLC patients.…”

Section: Introductionmentioning

confidence: 99%

Development and characterisation of disulfiram-loaded PLGA nanoparticles for the treatment of non-small cell lung cancer

Najlah

Ahmed

Iqbal

et al. 2017

European Journal of Pharmaceutics and Biopharmaceutics

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Non-Small Cell Lung Cancer (NSCLC) is the most common type of lung cancer in both men and women. A recent phase IIb study demonstrated that disulfiram (DSF) in combination with cisplatin and vinorelbine was well tolerated and prolonged the survival of patients with newly diagnosed NSCLC. However, DSF is rapidly (4 minutes) metabolised in the bloodstream and it is this issue which is limiting its anticancer application in the clinic. We have recently demonstrated that a low dose of DSF-loaded PLGA nanoparticles supplemented with oral Cu inhibited tumour growth and reduced metastasis in a xenograft mouse lung cancer model. Here we demonstrate the influence of PLGA polymer, stabilizer loading and molecular weight as well as sonication time on the characteristics, including DSF release and the cytotoxicity of 10% w/w DSF-loaded PLGA nanoparticles. The paper demonstrates that the choice of PLGA as no significant influence on the characteristics of the nanoparticles apart from their DSF release, which is due to the differing degradation rates of the polymers. However, increasing the loading and molecular weight of the stabilizer as well as the sonication time reduced the size of the nanoparticles, reduced their ability to protect the DSF from reacting with Cu and degrading in serum, while increasing their DSF release rate and cytotoxicity. Additionally, increasing the sonication time resulted in the premature degradation of the PLGA, which increased the permeability of the nanoparticles further decreasing their ability to protect DSF from reacting with Cu and degrading in serum, while increasing their DSF release rate and cytotoxicity.

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Cancer Stem Cells and Drug Resistance: The Potential of Nanomedicine

Cited by 422 publications

References 68 publications

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Ovarian cancer stem cells express ROR1, which can be targeted for anti–cancer-stem-cell therapy

Notch1-MAPK Signaling Axis is Essential in CD133+ Melanoma Initiating Cells

Development and characterisation of disulfiram-loaded PLGA nanoparticles for the treatment of non-small cell lung cancer

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