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- W4361238314 abstract "<div>Abstract<p>Emerging results indicate that cancer stem–like cells contribute to chemoresistance and poor clinical outcomes in many cancers, including ovarian cancer. As epigenetic regulators play a major role in the control of normal stem cell differentiation, epigenetics may offer a useful arena to develop strategies to target cancer stem–like cells. Epigenetic aberrations, especially DNA methylation, silence tumor-suppressor and differentiation-associated genes that regulate the survival of ovarian cancer stem–like cells (OCSC). In this study, we tested the hypothesis that DNA-hypomethylating agents may be able to reset OCSC toward a differentiated phenotype by evaluating the effects of the new DNA methytransferase inhibitor SGI-110 on OCSC phenotype, as defined by expression of the cancer stem–like marker aldehyde dehydrogenase (ALDH). We demonstrated that ALDH<sup>+</sup> ovarian cancer cells possess multiple stem cell characteristics, were highly chemoresistant, and were enriched in xenografts residual after platinum therapy. Low-dose SGI-110 reduced the stem-like properties of ALDH<sup>+</sup> cells, including their tumor-initiating capacity, resensitized these OCSCs to platinum, and induced reexpression of differentiation-associated genes. Maintenance treatment with SGI-110 after carboplatin inhibited OCSC growth, causing global tumor hypomethylation and decreased tumor progression. Our work offers preclinical evidence that epigenome-targeting strategies have the potential to delay tumor progression by reprogramming residual cancer stem–like cells. Furthermore, the results suggest that SGI-110 might be administered in combination with platinum to prevent the development of recurrent and chemoresistant ovarian cancer. <i>Cancer Res; 74(17); 4922–36. ©2014 AACR</i>.</p></div>" @default.
- W4361238314 created "2023-03-31" @default.
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- W4361238314 date "2023-03-30" @default.
- W4361238314 modified "2023-10-18" @default.
- W4361238314 title "Data from Epigenetic Targeting of Ovarian Cancer Stem Cells" @default.
- W4361238314 doi "https://doi.org/10.1158/0008-5472.c.6506573" @default.
- W4361238314 hasPublicationYear "2023" @default.
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