Immunotherapeutic Effect of EGCG and DAC Treatment for Triple Negative Breast Cancer
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 ... read moreinhibitors 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
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