In this narrative review, we summarize the role and significance of PI3K-AKT-mTOR (PAM) pathway in ovarian and endometrial cancers, providing the most recent and relevant literature on the topic and addressing options for targeting PAM along with future perspectives of drug development.
Although molecular characterization has been reported to customize therapeutic strategies and thereby improve therapeutic outcomes in EC, none of the targeted agents investigated (antiangiogenic and mTOR/PI3K pathway inhibitor agents) have resulted in a change in clinical practice in HR-EC.
Furthermore, we identified that CCL18 derived from TAMs upregulated KIF5B expression to promote EMT via activating the PI3K/AKT/mTOR signaling pathway in endometrial cancer.
On the whole, the findings of this study indicate that the inhibitory effects of miR195 on EC cell migration and invasion are associated with the PI3K/AKT signaling pathway and GPER expression.
Furthermore, HOTAIR activated the PI3K/Akt pathway to promote EC progression by suppressing PTEN <i>in vivo</i> Taking these results together, we revealed that high expression of HOTAIR promoted cell proliferation and inhibited apoptosis through activating the PI3K/Akt pathway via binding to PTEN, which might provide a prognostic marker and therapeutic target of EC.
Furthermore, genetic studies evaluated the effect of inflammatory cytokines secreted by visceral adipocytes in the modulation of angiogenesis and signaling pathways such as PI3K/AKT/mTOR, that result altered in the pathogenesis of EC.
More recently, molecular analysis of endometrial cancer revealed phosphorylation-dependent oncogenic signalling in the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways to be most frequently altered in type II ECs.
13 EC cell lines were profiled for their PI3K pathway and KRAS mutational and PTEN protein status and treated with one MEK- and two PI3K- targeted inhibitors alone and in combination.
Importantly, through western blot analysis, we found that inhibition of CLDN6 remarkably decreased p-AKT, p-PI3K, and mTOR expression level in EC HEC-1B cell line.
Taken together, our results showed that the formulation of BSYX had antitumor effect on endometrial cancer in vivo and in vitro and was related with FSH/PI3K/AKT/Gankyrin/HIF-<i>α</i>/cyclinD1 transduction pathway.
We attempt to investigate the effect of metformin on Ki-67, PI3K, p-AKT, p-S6K1, and p-4EBP1 staining in human endometrial cancer by immunohistochemical staining.
Together, these results suggest PI3K inhibition may be a plausible approach to expand the utility of PARP inhibitors to endometrioid endometrial cancers in a PTEN-deficient setting.
We assessed the sensitivity of endometrial cancer cell lines to PARP inhibitors (olaparib and BMN-673) and a PI3K inhibitor (BKM-120), alone or in combination, in the context of their PTEN mutation status.
Taken together, our findings suggest that PIK3CB/p110β contributes to some of the pleiotropic functions of PI3K in endometrial cancer, particularly in the early steps by contributing to cell proliferation.
Strikingly, coordinate knockdown of YAP and TAZ, mimicking activation of the HIPPO pathway, markedly decreased both constitutive and growth factor-induced PI3K pathway activation by decreasing levels of the GAB2 linker molecule in endometrial cancer lines.