Makii C, Ikeda Y, Oda K, et al. - Researchers used microarray data using 75 samples of clear cell ovarian carcinoma (CCOC) in order to gain clarity regarding the prognostic importance of PIK3CA and MDM2 expression in CCOC, and to gauge the potential curative influence of a dual inhibition of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) pathway and MDM2. In the expression array of 71 CCOCs, they found a significantly worse prognosis demonstrated by tumors with high expression of both PIK3CA and MDM2. In 4 CCOC cell lines without TP53 mutations, they noted the synergistic anti-proliferative influence of dual inhibition of the PI3K pathway by DS-7423 (dual inhibitor of pan-PI3K and mTOR) and MDM2 by RG7112 (MDM2 inhibitor). They also found that the combination therapy vs either single agent alone more robustly induced pro-apoptotic proteins (PUMA and cleaved PARP) with an increase of sub G1 population and apoptotic cells. In mice, a significant decrease in tumor volume without severe body weight loss was induced by the combination therapy. By immunohistochemistry from the xenograft tumors, vascularity and cell proliferation were significantly attenuated with the combination therapy, with an increase of apoptotic cell death. Based on these findings, experts concluded the potential promising therapeutic efficacy of a combination therapy targeting the PI3K pathway and MDM2 in CCOC.