1. University of Texas, Southwestern Medical Center, Dallas TX
Suppression of Radiation Induced c-Met Activation Leads to Radiosensitization of Prostate Cancer Cells
D. Gao, M. Bhuiyan, L. Yu, T. Takeshima, R. Hannan, J. T. Hsieh, D. Saha, D. W. Nathan Kim (will be presenting on behalf of D. Gao)
University of Texas, Southwestern Medical Center, Dallas TX
Number: 57041
Session title: Biology 1 - GI, GU, and Breast Cancers Date/Time:  :45 Location: Room D-2 Monitor number: 3 

2. Inhibition of c-Met by Cabozatinib leads to radio-sensitization of c-Met Expressing Prostate Cancer Cells

3. siRNA Silencing of Endogenous c-MET Leads to Radiation Sensitization of DU145 and PC3 cells.

4. Cabozatinib combined with radiation leads to tumor growth delay in c-Met expressing PC3 tumors, but not in c-Met deficient C4-2 tumors

5. c-Met inhibition leads to impaired DNA double strand break repair in DU 145 and PC3 cells

6. Conclusions
c-Met is differentially present in prostate cancer cells, and is activated/phosphorylated by radiation therapy
Inhibition of c-Met by Cabozatinib, or siRNA leads to radiosensitization.
Animal xenograft model demonstrates enhanced prostate tumor size reduction when IR is combined with Cabozatinib in c-Met expressing tumors
Mechanism of action of c-Met inhibition, may include impaired DNA double strand break repair kinetics
These preclinical data support consideration of clinical trials aimed at c-Met inhibition to augment RT response.