Patients with advanced prostate cancer frequently suffer from osteoblastic bone metastasis. A better understanding of the signaling circuitry involved in the interactions between tumor cells and osteoblasts is urgently needed to develop novel therapeutic approaches. The MDA PCa 118b prostate cancer cells can be used to model bone metastasis in the mouse since it has the unique feature to induce a strong osteoblastic reaction. Preliminary results show that this process involves the FGFR1/FGF-2 signaling axis, which is among the most frequently growth factor signaling pathways perturbed in advanced prostate cancer. Preliminary results pertaining to this application show that FGF-2/FGFR1 also play an important role in the development of numerical chromosomal imbalances (aneuploidy), which is detected in over 90% of patients with metastatic prostate cancer. In the present proposal, we aim to further interrogate the role of FGFR1/FGF-2 signaling using the mouse bone metastasis model and the FGFR-targeting agents TKI-258 (dovitinib) and AZD-4547.