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PI3K/Akt/mTOR Pathway Inhibitors in Cancer: A Perspective on Clinical Progress

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The phosphoinositide 3-kinase (PI3K)/serine-theronine protein kinase Akt (also known as protein kinase B (PKB))/mammalian target of rapamycin (mTOR) pathway is a vital transduction cascade that is connected with many essential cellular activities, such as growth and survival. Along with extensive pharmacological studies validating the therapeutic potential of targeting the PI3K/Akt/mTOR pathway for the treatment of cancer, kinase inhibitors targeting significant knots of this pathway including PI3K, Akt, mTOR, and 3-phosphoinositide-dependent protein kinase-1 (PDK-1) keep arising and entering clinical studies. Herein, we review the most up-to-date landscape on developing small-molecule kinase inhibitors targeting the PI3K/Akt/mTOR pathway, with emphasis on small-molecule inhibitors which have been progressed into clinical studies.

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Keywords: AGC; ATM; ATP; ATR; AZD-8055; Akt; Akt/PKB; BGT226; BKM-120; CAL-101; CCI-779; CLL; COX2; Celecoxib; DNA-PK; Erlotinib; FDA; FRAP1; GDC-0941; GPCRs; MTD; Mcl-1; NHL; Nilotinib; OSI-027; PDK-1; PH; PI-103; PI3K; PI3K INHIBITORS; PIKKs; PKA; PKB; PKC; PX-866; RAD-001; RCC; Rapamycin; Raptor; Rictor; S6Ks; SCCHN; SF-1126; SGK1; SMG-1; Sunitinib; TCN-PM; TRRAP; UCN-01; Vps34; XL-765; angiogenesis; apoptosis; cancer; cancer therapy; cell growth; clinical; eIF; etoposide; immunity; kinases; mTOR; malignancies; metabolism; migration; monotherapy; motility; mutation; perifosine; proliferation; small-molecule inhibitor; transcription; translation; triciribine phosphate; tumors; xenografts

Document Type: Research Article

Publication date: 2010-12-01

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