| Description |
-
Abstract: Triple negative breast cancer (TNBC) is defined by lack of ER, PR or overexpression of Her2. Therefore TNBC is refractory to targeted treatments for the other classes of breast cancer. The Wnt/β-catenin signaling pathway has elevated activity in TNBC, and the Wnt repressor HBP1 is decreased in TNBC. Therefore, the Yee lab sought mechanistic treatments to induce expression of Wnt inhibito... read morers in the TNBC setting. DAC (5-aza-2'-deoxycytidine) is an inhibitor of DNA methylation through inhibiting DNA Methyltransferase 1 (DNMT1), and treatment with DAC restores epigenetically silenced genes such as HBP1, leading to increased expression. In addition, EGCG (epigallocatechin 3-gallate) has been shown to induce HBP1 expression levels through an RNA stabilization mechanism. The Yee lab has used the drug combination of EGCG and DAC to effectively decreases both tumor size and the incidence of metastases in xenograft mouse models of high Wnt signaling/TNBC. Here, I demonstrate that EGCG/DAC treatment unexpectedly alters the immune presentation pathway in tumors, suggesting that EGCG/DAC might be effective as an adjuvant therapy in combination with immune checkpoint treatments such as Pembrolizumab.
Thesis (M.S.)--Tufts University, 2018.
Submitted to the Dept. of Pharmacology and Drug Development.
Advisors: Amy Yee, and Eric Paulson.
Keyword: Pharmacology.read less
|
|---|
This object is in collection
