Choi HJ, et al. - Since PI3K/mTOR pathway represents a key signaling pathway involved in drug resistance of ovarian cancer cells, researchers assessed the impact of a newly developed PI3K/mTOR dual inhibitor, CMG002, on chemoresistant ovarian cancer cells. They performed in vitro and in vivo studies on PTX-resistant SKpac17 or cisplatin-resistant A2780cis ovarian cancer cells and a xenograft mouse model, respectively. They evaluated expression of PI3K, p-mTOR, p-Akt, p-S6, Bim, and caspase-3 via Western blot analysis. Findings revealed a marked attenuation in tumor growth by treatment with CMG002, either alone or in combination with paclitaxel or cisplatin, as seen in in-vivo xenograft studies. Findings in both in vitro and in vivo analyses revealed marked suppression of mTOR (Ser2448), Akt (Ser473), Akt (Thr308), and S6 (Ser235/236) phosphorylation by CMG002. Overall, CMG002 (a very potent PI3K/mTOR dual inhibitor)-induced cytotoxicity was seen in chemoresistant ovarian cancer cells. Based on the findings, the potential utility of this novel inhibitor as a new therapeutic strategy for chemoresistant ovarian cancer was demonstrated.