Preventive administration of ARRY-470 therapy reduces sarcoma-induced nerve sprouting of CGRP+ and NF200+ nerve fibers. At day 20 post cell injection, the density of CGRP+ (A), NF200+ (B) nerve fibers is significantly greater in sarcoma + vehicle-treated mice compared to sham + vehicle-treated mice. This tumor-induced nerve sprouting is significantly attenuated by early/sustained administration of ARRY-470 (30 mg/kg; p.o., BID) initiated at day 6 and maintained through day 20 post tumor cell injection), but not by late/acute (30 mg/kg; p.o., BID given at day 18 and maintained through day 20 post tumor cell injection) administration of ARRY-470. Nerve fiber density was determined by measuring the total length of nerve fibers per unit volume in the periosteum. Bars represent the mean ± SEM. *p < 0.05 vs. sham + vehicle, # p < 0.05 vs sarcoma + vehicle. The number of animals was n = 8 for sham, n = 9 for sarcoma + vehicle, n = 9 for sarcoma + early/sustained ARRY-470, and n = 7 for sarcoma + late/acute ARRY-470.