Immunotherapeutic Effect of EGCG and DAC Treatment for Triple Negative Breast Cancer
Li, Kaiqi.
2018
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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 inhi... read morebitors 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 - ID:
- rn301c498
- Component ID:
- tufts:25425
- To Cite:
- DCA Citation Guide EndNote
