MDM2 appears to be a immediate target of effective AKT that triggers its phosphorylation activation and translocation to the nucleus, ergo resulting in p53 loss. Given that chemotherapies normally trigger the PI3K/Akt route, using PI3K inhibitors may decrease the susceptibility of cancer cells to produce resistance. d in certain tyrosine kinase receptors appeared as a significant type of targets for drug design in cancer. Several protein kinase inhibitors are now in clinical trial Everolimus 159351-69-6 and the achievement of a number of them, including Gleevec for the treatment of chronic myeloid leukaemia, Iressa for lung cancer and Herceptin for breast cancer, has confirmed this method. Nonetheless a growing issue, accompanying to administration of these drugs, is the development of resistance which could compromise the treatment. Among the most calm activities that plays a role in this disappointing approach may be the tendency of cancer cells to stimulate the path, alone from RTKs signalling. Consequently PI3Ks represent an attractive target for the design of small molecule inhibitors preventing the downstream activation of several protein kinases such as mTOR, AKT, PDK1 and p70S6K. Experimental studies have shown the potential benefit of the initial generation PI3K inhibitors including Wortmannin and LY294002. PI3K inhibitors present anti proliferative or professional apoptotic effects in a number of Plastid tumefaction types. Despite the role of LY294002 and wortmannin in understanding PI3K function, their functionality in medical practice is affected by their bad selectivity, their inability to discriminate various PI3K isoforms and their accumulation. Recently, in attempt to improve selectivity, a second generation of inhibitors that’ll exhibit decreased toxicity without affecting the efficiency is discovered. For example, the PI 103 substance was found to prevent all four type I PI3Ks and the mammalian target of rapamycin. PI 103 shows antitumor activity by inhibiting tumor cell invasion in vitro as well as in vivo and by preventing vascularization in human tumor xenograft models. Particular inhibitors with growing selectivity over different PI3K isoforms are also tested: apparently, stopping different PI3K isoforms show different efficiency in different cancers. As an example, ALK inhibitor TGX115 or PIK 90 show different results in glioma cells. Surprisingly TGX 115, affects AKT phosphorylation nonetheless it doesn’t make appropriate anti proliferative effects. On the other hand, administration of PIK 90 important but limited efficacy in blocking proliferation, nonetheless, a combinatorial inhibition of mTOR and p110 showed the efficacy. The possible negative effects need to be considered, especially for long term chronic treatment, though these inhibitors are most likely planning to give a powerful system for cancer therapy.