The phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patients

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dc.contributor.authorMartelli, Alberto M.
dc.contributor.authorEvangelisti, Camilla
dc.contributor.authorChiarini, Francesca
dc.contributor.authorMcCubrey, James A.
dc.date.accessioned2016-06-16T17:18:48Z
dc.date.available2016-06-16T17:18:48Z
dc.date.issued2010-06
dc.description.abstractThe phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling axis plays a central role in cell proliferation, growth, and survival under physiological conditions. However, aberrant PI3K/Akt/mTOR signaling has been implicated in many human cancers, including acute myelogenous leukemia (AML). Therefore, the PI3K/Akt/mTOR network is considered as a validated target for innovative cancer therapy. The limit of acceptable toxicity for standard polychemotherapy has been reached in AML. Novel therapeutic strategies are therefore needed. This review highlights how the PI3K/Akt/mTOR signaling axis is constitutively active in AML patients, where it affects survival, proliferation, and drug-resistance of leukemic cells including leukemic stem cells. Effective targeting of this pathway with small molecule kinase inhibitors, employed alone or in combination with other drugs, could result in the suppression of leukemic cell growth. Furthermore, targeting the PI3K/Akt/mTOR signaling network with small pharmacological inhibitors, employed either alone or in combinations with other drugs, may result in less toxic and more efficacious treatment of AML patients. Efforts to exploit pharmacological inhibitors of the PI3K/Akt/mTOR cascade which show efficacy and safety in the clinical setting are now underway.en_US
dc.identifier.citationOncotarget; 1:2 p. 89-103en_US
dc.identifier.issn1949-2553
dc.identifier.pmidpmc2911128en_US
dc.identifier.urihttp://hdl.handle.net/10342/5656
dc.relation.urihttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2911128/en_US
dc.subjectPI3K/Akt/mTORen_US
dc.subjectleukemiaen_US
dc.subjectleukemic stem cellsen_US
dc.subjectsignal transduction modulatorsen_US
dc.subjecttargeted therapyen_US
dc.subjectcombination therapyen_US
dc.titleThe phosphatidylinositol 3-kinase/Akt/mTOR signaling network as a therapeutic target in acute myelogenous leukemia patientsen_US
dc.typeArticleen_US
ecu.journal.issue2en_US
ecu.journal.nameOncotargeten_US
ecu.journal.pages89-103en_US
ecu.journal.volume1en_US

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