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PI3K-AKT-mTOR and NFκB Pathways in Ovarian Cancer: Implications for Targeted Therapeutics
1Departments of Cancer Biology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA.
Abstract:
Ovarian cancer is the most lethal gynecologic malignancy in the United States, with an estimated 22,530 new cases and 13,980 deaths in 2019. Recent studies have indicated that the phosphoinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR), as well as the nuclear factor-κ light chain enhancer of activated B cells (NFκB) pathways are highly mutated and/or hyper-activated in a majority of ovarian cancer patients, and are associated with advanced grade and stage disease and poor prognosis. In this review, we will investigate PI3K/AKT/mTOR and their interconnection with NFκB pathway in ovarian cancer cells.
Insights
Ovarian cancer, a lethal malignancy, often involves mutated phosphoinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) and nuclear factor-κ light chain enhancer of activated B cells (NFκB) pathways. This review explores their interconnection in ovarian cancer progression.
Area of Science:
- Gynecologic Oncology
- Molecular Biology
- Cancer Signaling Pathways
Background:
- Ovarian cancer is a leading cause of cancer death in the United States.
- The phosphoinositol 3 kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is frequently dysregulated in ovarian cancer.
- The nuclear factor-κ light chain enhancer of activated B cells (NFκB) pathway is also implicated in ovarian cancer pathogenesis.
Purpose of the Study:
- To review the role of the PI3K/AKT/mTOR pathway in ovarian cancer.
- To investigate the interconnection between the PI3K/AKT/mTOR and NFκB pathways in ovarian cancer.
- To understand the association of these pathways with advanced disease and poor prognosis.
Main Methods:
- Literature review of recent studies on PI3K/AKT/mTOR and NFκB pathways in ovarian cancer.
- Analysis of mutation and hyper-activation data for these pathways in ovarian cancer patients.
- Examination of the relationship between pathway activation, disease grade, stage, and prognosis.
Main Results:
- The PI3K/AKT/mTOR pathway is highly mutated and/or hyper-activated in a significant proportion of ovarian cancer cases.
- The NFκB pathway also shows frequent alterations in ovarian cancer.
- Dysregulation of both pathways is associated with advanced stage, high grade, and poor patient outcomes.
Conclusions:
- The PI3K/AKT/mTOR and NFκB pathways represent critical signaling networks in ovarian cancer.
- Understanding the interplay between these pathways is crucial for developing targeted therapies.
- Targeting these interconnected pathways may offer new therapeutic strategies for ovarian cancer patients.
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