SKI-606, an Src Inhibitor, Reduces Tumor Growth, Invasion, and Distant Metastasis in a Mouse Model of Thyroid Cancer

KIM WON GU; GUIGON CELINE; FOZZATTI LAURA; PARK JEONG WON; LU CHANGXUE; WILLINGHAM MARK C; CHENG SHEUE-YANN

AMER ASSOC CANCER RESEARCH

Lugar: Philadelphia; Año: 2012 p. 1281 - 1281

Purpose: Src is overexpressed or hyperactivated in a variety of human cancers, including thyroid carcinoma. Src is a central mediator in multiple signaling pathways that are important in oncogenesis and cancer progression. In this study, we evaluated the effects of an Src inhibitor, SKI-606 (bosutinib), in a spontaneous metastatic thyroid cancer model with constitutively activated Src (ThrbPV/PVPten þ/ mice). Experimental Design: ThrbPV/PVPtenþ/ mice were treated with SKI-606 or vehicle controls, beginning at6 weeks of age until the mice succumbed to thyroid cancer. We assessed the effects of SKI-606 on thyroid cancer progression and analyzed the impact of SKI-606 on aberrant Src-mediated signaling.Results: SKI-606 effectively inhibited aberrant activation of Src and its downstream targets to markedly inhibit the growth of thyroid tumor, thereby prolonging the survival of treated mice. While Src inhibition did not induce cell apoptosis, it decreased cell proliferation by