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Copyright ©The Author(s) 2015.
World J Gastroenterol. Nov 21, 2015; 21(43): 12261-12273
Published online Nov 21, 2015. doi: 10.3748/wjg.v21.i43.12261
Table 1 Role of Akt in regulating cell cycle
Cell cycle regulation by Akt upon mitogen stimulation
Cell cycle phaseDirect regulationIndirect regulationDownstream effect
G1 → S phaseP-p21 at Thr145 residue[107]↑ Transcription of c-MYC[108]Increase in CyclinD expression
Decrease in cdk inhibitors: p21cip1, p21kip1, p15INK4B
G2 → M phaseP-Cdc25B at Ser353[109]Cdc-25B inactivation
Cyclin B activation
P-Wee1Hu at Ser642[110]Inactivation of Wee1Hu results in G2/M cell cycle progression
P-Myt1 at Ser75[111]Activation of Cyclin B-associated Cdk1 kinase activity
S → G2 phaseP-Cdk2 at Thr39[112]Cytoplasmic shuttling of Cdk2
Table 2 Summary of phosphatidylinositol-3 kinases/Akt/mTOR inhibitors under investigation for gastric cancer treatment
Classification of PI3K/Akt/mTOR inhibitorsInhibitors under investigation for GCClinical status for GC
PI3K inhibitors: 3 classes of PI3K inhibitors
Pan-class I inhibitorsPX-866Phase-II study for solid tumors
NVP-BKM120Phase-I study for advanced solid tumors
ZSTK474Preclinical studies
BAY80-6946Phase-II study for advanced solid tumors
Isoform specific PI3K inhibitorsBYL719Phase-I study
INK117Phase-I study
Dual Akt/mTOR inhibitorsNVP-BEZ235Preclinical studies
VS-5884Phase-II study
PI-103Phase-I study
Akt inhibitorsAZD5363Preclinical studies
MK-2206Phase-II study
PerifosinePreclinical studies
TCN-PMPhase-I study for solid tumors
mTOR inhibitors: 2 types
RapalogsEverolimusPhase-III study
RidaforolimsPreclinical studies
SirolimusPhase-I study
TemsirolimusPhase-II study
mTORC1/2 inhibitorsPP242Preclinical studies