PI3K/AKT/mTOR inhibitors in ovarian cancer.
Phisiological activation of PI3K pathway is necessary for cells to regulate many different physiological processes such as transcription, protein synthesis, metabolic responses and membrane trafficking. Abnormal activation of the PI3K pathway leads to an increased activity resulting in tumor onset, maintenance, progression and invasion. Both genetic and epigenetic alterations could affect the normal pathway's activation. Ovarian cancer is the leading cause of death from gynaecological malignancies in the western world. PI3K pathway has been recorded as one of the most deregulated signalling pathway in many tumors, including ovarian ones. So it could be considered an attractive target to be investigated with the various classes of chemical compounds already present or in development. In this rewiew we'll try to discuss the published data of the inhibitors targeting members of the PI3K/ akt/ mTOR pathway in the ovarian cancer setting from a preclinical and clinical point of view, with particular emphasis on drugs combination and strategies of administration. Relevant issues and limitations to the use of particular compounds will be also addressed.
Laboratory of Molecular Pharmacology, Dept of Oncology, Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
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Mazzoletti
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Broggini
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases