TGF-β receptor I kinase inhibitor combinatorial treatment with radiation inhibits tumor growth and metastasis in syngeneic breast mouse models

Global Summit on Oncology & Cancer

May 25-27, 2017 Osaka, Japan

Yhun Y Sheen, Ji Y Park and Ji W Choe

College of Pharmacy- Ewha Womans University, Korea

Posters & Accepted Abstracts: J Cancer Sci Ther

Abstract :

EW-7197, TGF-�² receptor I kinase inhibitor combinatorial treatment with radiation inhibits tumor growth and metastasis in syngeneic breast mouse models. Radio-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 upregulation of TGF-�² 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 cells, 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 fractionatedradiation (total dose 12 Gy, 4 Gy X3) with or without the combinatorial treatment of EW-7197 (2.5 mg/kg). Combinatorial treatment of EW-7197 synergistically reduced the primary tumor size when combined with radiation and inhibits lung metastasis efficiently. This effect of 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.

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).

Email: yysheen@ewha.ac.kr