Perspectives on targeting the phosphatidylinositol 3-kinase pathway for personalized medicine in endometrial and ovarian cancers

Publication date: Available online 11 May 2016 Source:Personalized Medicine Universe Author(s): Katsutoshi Oda, Yuji Ikeda, Tomoko Kashiyama, Aki Miyasaka, Kanako Inaba, Yuichiro Miyamoto, Osamu Wada-Hiraike, Kei Kawana, Yutaka Osuga, Tomoyuki Fujii Endometrial and ovarian cancers show similar genetic and pathological backgrounds. In particular, high frequencies of activating mutations in the phosphatidylinositol 3-kinase (PI3K) pathway, including mutations in PIK3CA and PTEN, are found in both estrogen-dependent endometrial cancer (type I endometrioid carcinomas) and ovarian clear cell and endometrioid carcinomas. In this review, we focus on the PI3K pathway as a potential molecular target for personalized therapies in endometrial and ovarian cancers. We found that targeting the PI3K/mammalian target of rapamycin (mTOR) pathway produced anti-tumor effects in endometrial cancer upon suppression of the PI3K pathway. The presence of KRAS mutations may be a marker for resistance to the inhibition of the PI3K/mTOR pathway. However, the combination of a PI3K/mTOR pathway inhibitor and a MAPK pathway inhibitor, such as a MEK inhibitor, has been shown to suppress cell proliferation synergistically in certain endometrial cancers. In addition, PI3K/mTOR pathway inhibition sensitized endometrial cancer cells to ionizing radiation and produced anti-tumor effects in ovarian clear cell carcinomas in both in vitro and in vivo studies. Moreover, inhibition reduced ...
Source: Personalized Medicine Universe - Category: Drugs & Pharmacology Source Type: research