gsk-2126458 and Carcinoma--Ovarian-Epithelial

The PI3K/AKT/mTOR pathway is one of the most highly activated cellular signaling pathways in advanced ovarian cancer. Although several PI3K/AKT/mTOR inhibitors have been developed to treat various types of cancer, the antitumor efficacy of many of these compounds against ovarian cancer has remained unclear.. Here, we tested and compared a panel of 16 PI3K/AKT/mTOR inhibitors (XL765, Miltefosine, Rapamycin, CCI-779, RAD001, FK506, XL147, GSK2110183, IPI-145, GSK2141795, BYL719, GSK458, CAL-101, XL765 analogue SAR245409, Triciribine, and GDC0941) that have entered clinical trials for antitumor activity against ovarian cancer, as well as the front line drug, paclitaxel. Antitumor efficacy was measured in both ovarian cancer cell lines and patient-derived ovarian primary tumor cell lines in vitro and in vivo.. Based on our results, we conclude that GSK458 may serve as an attractive candidate to treat ovarian cancer.

Topics: Animals; Carcinogenesis; Carcinoma, Ovarian Epithelial; Cell Line, Tumor; Cell Proliferation; Cells, Cultured; Female; Humans; Mice; Mice, Nude; Ovarian Neoplasms; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Protein Kinase Inhibitors; Pyridazines; Quinolines; Sulfonamides; TOR Serine-Threonine Kinases; Xenograft Model Antitumor Assays