Makii C, Ikeda Y, Oda K, et al. - Whether PIK3CA and MDM2 expression hold prognostic significance in clear cell ovarian carcinoma (CCOC) and whether dual inhibition of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and MDM2 has any potential therapeutic effect, was investigated. Researchers used 75 samples of CCOC and assessed cDNA expression using microarray data. They found that significantly worse prognosis was shown by tumors with high expression of both PIK3CA and MDM2 in expression array of 71 CCOCs. In 4 CCOC cell lines without TP53 mutations, synergistic anti-proliferative impact was observed following dual inhibition of the PI3K pathway by DS-7423 (dual inhibitor of pan-PI3K and mTOR) and MDM2 by RG7112 (MDM2 inhibitor). More robust induction of pro-apoptotic proteins (PUMA and cleaved PARP) with a rise in sub G1 population and apoptotic cells were seen in relation to treatment with combination therapy vs either single agent alone. A significant decrease in tumor volume without severe body weight loss was seen in mice treated with the combination therapy. Overall, experts viewed targeting the PI3K pathway and MDM2 by a combination therapy as a possible promising therapeutic strategy in CCOC.