Accession Number:
AD1160522
Title:
Targeting the Mevalonate Pathway and Its Restorative Feedback Loop in Breast Cancer
Descriptive Note:
[Technical Report, Final Report]
Corporate Author:
UNIVERSITY HEALTH NETWORK TORONTO (ONTARIO)
Personal Author(s):
Report Date:
2021-07-01
Pagination or Media Count:
122
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 dipyridamoleDP 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.
Descriptors:
Subject Categories:
- Medicine and Medical Research