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Accession Number:

AD1160522

Title:

Targeting the Mevalonate Pathway and Its Restorative Feedback Loop in Breast Cancer

Author(s):

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Report Date:

2021-07-01

Abstract:

We have shown that targeting the mevalonate pathway with fluvastatin preferentially induces apoptosis in breast cancer (BrCa) cells that have undergone epithelial-to-mesenchyme transition (EMT), a critical process for the initiation of metastasis. Moreover, we have identified that EMT gene expression is bimodally distributed and is a biomarker of fluvastatin sensitivity. Mechanistically, we have shown that fluvastatin can induce apoptosis by limiting production of an important end-product of the mevalonate pathway essential for protein N-glycosylation associated with EMT. We have also shown that dipyridamole(DP) potentiates fluvastatin-induced apoptosis of BrCa cells by blocking the statin-induced restorative feedback loop. We have also identified additional agents that can potentiate statin-induced BrCa cell death, thereby expanding this class of anti-cancer agents. We have published 3 manuscripts (2 at Cancer Research and Molecular Oncology), have another nearly ready for resubmission to Nature Communications, and have published a review article in Clinical Cancer Research. Thus, we have been highly productive and made advances that are actionable and have potential to immediately impact BrCa patient outcome.

Pages:

122

File Size:

12.38MB

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Distribution Statement:

Approved For Public Release

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