Significance of the hedgehog (Hh) pathway in ovarian cancer xenograft growth.

5058 Background: Initial immunohistochemical analysis revealed that about 50% of ovarian cancer samples expressed sonic Hh ligand in the tumor epithelium, suggesting this signaling pathway might be active in this disease. Thus we examined the activity of IPI-926, a potent inhibitor of the Hh pathway that blocks the activity of Smoothend, in a preclinical model of serous ovarian cancer in an adjuvant and maintenance setting. Methods: Primary human serous ovarian tumor xenograft tissue was utilized to generate tumor explants in NOD/SCID mice. Mice bearing tumors (250-1900 mm3) were randomized into four groups 1) IPI-926 PO gavage q 24 hours along with intraperitoneal (IP) vehicle; 2) paclitaxel and carboplatinum (T/C) IP q 7 days with vehicle by PO gavage q 24 hours; 3) IPI-926 by PO gavage q 24 hours + IP T/C; 4) vehicle by PO gavage q 24 hours + IP vehicle q 7 days. The adjuvant treatment period spanned 19 days. In the maintenance arms of the experiment, T/C treatment was stopped in the two groups receivi...