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Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer,therapeutic treatment options for platinum-resistant ovarian cancer

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Cancer Drug Resistance 2021年第3期4卷 573-595页

作者： Natasha Rinne Elizabeth LChristie anastasia ardasheva Chun Hei Kwok Nikita Demchenko Caroline Low Catherine Tralau-Stewart Christina Fotopoulou Paula Cunnea Department of Surgery&Cancer Imperial College LondonHammersmith campusLondon W120NNUK Peter MacCallum Cancer Centre East MelbourneVictoria 3002Australia Department of Metabolism Digestion&Reproduction Imperial College LondonLondon W120NNUK Takeda Academic Innovation Center for External InnovationTakeda CaliforniaSan DiegoCA 92121USA

The survival rates for women with ovarian cancer have shown scant improvement in recent years,with a 5-year survival rate of less than 40%for women diagnosed with advanced ovarian ***-grade serous ovarian cancer(HGSOC)is the most lethal subtype where the majority of women develop recurrent disease and chemotherapy resistance,despite over 70%-80%of patients initially responding to platinum-based *** phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signaling pathway regulates many vital processes such as cell growth,survival and ***,this pathway is frequently dysregulated in cancers including different subtypes of ovarian cancer,through amplification or somatic mutations of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),amplification of AKT isoforms,or deletion or inactivation of *** evidence indicates a role for the PI3K/AKT/mTOR pathway in the development of chemotherapy resistance in ovarian ***,targeting key nodes of the PI3K/AKT/mTOR pathway is a potential therapeutic *** this review,we outline dysregulation of PI3K signaling in ovarian cancer,with a particular emphasis on HGSOC and platinum-resistant *** review pre-clinical evidence for inhibitors of the main components of the PI3K pathway and highlight past,current and upcoming trials in ovarian cancers for different inhibitors of the *** no inhibitors of the PI3K/AKT/mTOR pathway have thus far advanced to the clinic for the treatment of ovarian cancer,several promising compounds which have the potential to restore platinum sensitivity and improve clinical outcomes for patients are under evaluation and in various phases of clinical trials.

关键词： Ovarian cancer high-grade serous PI3K/AKT/mTOR pathway chemotherapy resistance inhibitors therapeutics

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