PI3K/AKT/mTOR Pathway in Ovarian Cancer Treatment: Are We on the Right Track?

Abstract

The high recurrence rate and the low overall survival in ovarian cancer suggest that a more specific therapeutic approach in addition to conventional treatment is required. Translational and clinical research is investigating new molecular targets in order to find an alternative way to affect tumor growth and to minimize the overlap of toxicity of antiblastic agents. Given its implication in many cellular activities including regulation of cell growth, motility, survival, proliferation, protein synthesis, autophagy, transcription, as well as angiogenesis, PI3K/AKT/mTOR is one of the most investigated intracellular signaling pathways. A dis-regulation of this pathway has been shown in several tumors, including ovarian cancer. In this setting, mTor proteins represent a potential target for inhibitors, which could ultimately play a pivotal role in counteracting cellular proliferation. Recently, mTor inhibitors have been approved in the treatment of pancreatic neuroendocrine tumors, mantle cell lymphoma and renal cancer. Clinical trials have assessed the safety of these drugs in ovarian cancer patients. Ongoing phase I and II studies are evaluating the oncologic outcome of mTor inhibitor treatment and its effect in combination with conventional chemotherapy and target agents.

Laminarin-Derived from Brown Algae Suppresses the Growth of Ovarian Cancer Cells via Mitochondrial Dysfunction and ER Stress

“…Laminarin inhibits the activity of p-AKT and p-ERK1/2 signaling proteins in human liver cancer and melanoma [22,23]. In addition, a blockade of PI3K and MAPK signaling is considered a novel therapeutic strategy to treat OC [31,32]. Likewise, in the present study, laminarin significantly decreased the phosphorylation of PI3K/MAPK signaling proteins in both OC cells.…”

Identification of Ovarian Cancer Gene Expression Patterns Associated with Disease Progression and Mortality

“…Mutations in BRCA1 and BRCA2 is experimentally implicated in OC Sowter and Ashworth (2005). The PI3K/AKT/mTOR pathway is activated in approximately 70% of ovarian cancer cases (Gasparri et al (2017)). From KEGG pathway analysis, BRCA1 was found to be involved in PI3K/AKT/mTOR pathway.…”

The impact of ultraviolet- and infrared-based laser microdissection technology on phosphoprotein detection in the laser microdissection-reverse phase protein array workflow

“…1). The levels of ten key phosphoproteins involved in PI3K/AKT/mTOR signal transduction and related pathways which are frequently activated in ovarian cancer [59,60] were analyzed using a standardized analytical panel of antibodies [58] (Additional file 1: Table S1). Comparative analyses revealed that the abundance level of all phosphoproteins remained consistent between the UV-and IR-mediated harvests (Fig.…”