activity of GSK3 was found to be required for GC induced apoptosis. GSK3 inhibitors avoided GC induced apoptosis, and GC weight frequently occurs through inhibition of GSK action. ATP-competitive ALK inhibitor Reactivating GSK3 by utilizing inhibitors of the PI3K Akt or mTOR pathways sensitized GC resistant cells to GC induced apoptosis. GSK3 was found to communicate with GR in the absence of ligand and produced from GR following experience of GC. GC treatment led to interaction of both GSK3 and GSK3 with Bim. GSK3 also adjusts GR transcriptional activity of Bim, IAP1, and GILZ. is effect of GSK3 on GR transactivation was independent of known GSK3 phosphorylation sites. GSK3 was also shown to be involved with GC induced bone lost. PI3K/Akt and mTOR signaling pathways Retroperitoneal lymph node dissection are frequently hyperactivated in GC resistant T ALL and is associated with poor prognosis and chemotherapeutic resistance in pediatric B precursor ALL. mTOR is really a essential regulator of cell metabolism, development, and proliferation and mTOR is positively regulated by PI3K/Akt and Notch1, while negatively regulated by the tuberous sclerosis tumefaction suppressor complex. mTORC2 activity was essential for Notchdriven T lymphomagenesis. Activation of mTOR contributes to tumefaction cell survival in ALK good ALCL, mantle cell lymphoma, youth T precursor ALL, T ALL, and AML. Akt and mTOR confer drug resistance by phosphorylating a number of objectives. Phosphorylation and inactivation of GSK3 is a important cause for GC resistance that can be overcome by reactivating GSK3, for example, by Akt inhibitors or mTOR inhibitors. the mTOR inhibitor Rapamycin is effective in overcoming GC weight order Cathepsin Inhibitor 1 in a variety of lymphoid malignancies. GC weight can be overcome in Akt lively lymphoma cells by inhibiting Src members, PI3K, or an Akt inhibitor. Combination of GC with rapamycin or GC with Obatoclax resulted in paid off Akt phosphorylation at Ser473, indicating that mTOR might also act upstream to Akt. mTORC1 facilitates r308 phosphorylation by PDK1 and immediately phosphorylates Akt/PKB on Ser473. GCs may possibly also independent of other cytotoxic agents lower mTOR activity in lymphoid cells. Low-dose arsenic trioxide could sensitize GC resistant ALL to Dex through an Akt dependent process. Inhibition of mTOR with rapamycin, which binds to FKBP12, overcomes Ras dependent emergency signals and leads to increased Bim expression. Synergy between mTOR inhibitors and CCI 779 and other chemotherapeutic agents is seen in Band T lineage ALL cell lines and preclinical models. Akt exercise is negatively regulated by PTEN, a tumefaction suppressor gene that’s suppressed, mutated, or deleted at high frequency in a great number of cancers.