Effects of EGCG and DAC Combinational Treatment on Treating Triple Negative Breast Cancer and Aiding Immune Checkpoint Blockage Therapies
Wang, Zixu.
2019
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Triple-negative breast
cancer (TNBC) is a type of breast cancer that has decreased expression of progesterone
receptor (PR) and estrogen receptor (ER), with no overexpression level of human
epidermal growth factor receptor 2 (Her2). TNBC is most difficult to treat due to lack
of druggable targets, high rates of recurrence and metastasis and resistance to
immunotherapy. One of the common changes ... read moreobserved in TNBC is activation of Wnt
signaling. Based on prior work, the Yee lab designed a combinational therapy that was
likely to activate inhibitors of Wnt signaling and potentially alter TNBC.
Epigallocatechin-3-gallate (EGCG) and decitabine (DAC), prior studies using this
combination showed reduce Wnt signaling, inhibition of TNBC tumor growth and reduced
distal metastasis. In this study, we show EGCG/DAC treatment of mouse models of TNBC
increases immunogenicity, including 1) immune cell infiltration into the tumor
microenvironment, 2) up-regulation of IFN signaling, 3) increased expression of viral
mimicry genes. Furthermore, EGCG/DAC increases E-cadherin expression, suggesting a
mechanism of the reduction in metastasis. In conclusion, EGCG/DAC treatment inhibits
TNBC tumor growth, inhibits Wnt signaling, and regulates expression of immune
checkpoints on both T cells and tumor cells, making EGCG/DAC a possible adjuvant for
immune checkpoint therapy.
Thesis (M.S.)--Tufts University, 2019.
Submitted to the Dept. of Pharmacology and Drug Development.
Advisor: Amy Yee.
Committee: Eric Paulson.
Keyword: Pharmacology.read less - ID:
- mc87q3771
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