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Journal of Clinical & Experimental Pathology | ISSN: 2161-0681 | Volume 8
Breast Pathology and Cancer Diagnosis
6
th
World Congress and Expo on
July 25-26, 2018 | Vancouver, Canada
Medicinal Chemistry and Rational Drugs
20
th
International Conference on
&
Vactosertib, ALK5 inhibitor combinatorial treatment with radiation inhibits lung metastasis in
syngeneic breast mouse models
Yhun Y Sheen
Ewha Womans University, Korea
R
adio-resistance and relapse after chemotherapy is a life-threatening problem for breast cancer patients. We identified the
molecular signatures of the recurrent breast cancer patients after radiotherapy, which showed the up-regulation of TGF-β
signaling and the epithelial-to-mesenchymal transition (EMT). In order to find the potential therapeutic strategies to improve
radiation therapy, we conducted gene set enrichment analysis, a computational method that determines whether an a priori
defined gene set shows statistically significant between two phenotypes, using the breast cancer clinical data with Servant
cohort (GSE30682). Since we have proved that EW-7197 showed the inhibitory effect
in vivo
in various breast cancer mouse
models previously, we carried out experiments that might test if combinatorial treatment of EW-7197 improves radiation
therapy using two syngeneic mouse models. Met 1 cell, which are derived from primary tumors of the FVB/N transgenic
mouse with mammary tumor-polyoma virus middle T antigen (MMTV-PyVmt), were injected to fourth inguinal fat pads of
FVB/N mice. 4T1 cells, which are derived from primary tumors of Balb/c mice, were injected as same way into Balb/c mice. Mice were
treated with the fractionated-radiation (total dose 12 Gy, 4 Gy X3) with or without the combinatorial treatment of EW-7197 (2.5 mg/kg).
Conclusion & Significance: Vactosertib (EW-7197), ALK5 inhibitor combinatorial treatment with radiation inhibits tumor
growth and metastasis in syngeneic breast mouse models. This effect of Vactosertib (EW-7197), ALK5 inhibitor combinatorial
treatment with radiation inhibits tumor growth and metastasis in syngeneic breast mouse models. Vactosertib (EW-7197)
maybe related to the breast cancer stem-like phenotype, which is increased by 4Gy irradiation
in vitro
. We need to further
study to conclude the therapeutic mechanisms of EW-7197 on improving radiation therapy. This work was supported by the
National Research Foundation of Korea grant funded by the Korea government (NRF-2015M2A2A7A01041499) and (NRF-
2014R1A1A2005644).
Biography
Yhun Sheen has her research interest in developing new anti-cancer drug. She had participated in the development of TEW-7197 which is currently under clinical
trial in USA (NCT02160106).
yysheen@ewha.ac.krYhun Y Sheen, J Clin Exp Pathol 2018, Volume 8
DOI: 10.4172/2161-0681-C3-052