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

P.      Wu; Y.-Z.      Hu

doi:10.2174/092986710793361234

Abstract

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.

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