Transcript Inhibition of c-Met by Cabozatinib leads to radio

Suppression of Radiation Induced cMet 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: 2014-09-14 16:45
Location: Room D-2
Monitor number: 3
Inhibition of c-Met by Cabozatinib leads to
radio-sensitization of c-Met Expressing
Prostate Cancer Cells
siRNA Silencing of Endogenous c-MET Leads
to Radiation Sensitization of DU145 and PC3
cells.
Cabozatinib combined with radiation leads to tumor
growth delay in c-Met expressing PC3 tumors, but not in
c-Met deficient C4-2 tumors
c-Met inhibition leads to impaired DNA double strand
break repair in DU 145 and PC3 cells
Conclusions
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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.