PI3K inhibitors
Phosphatidylinositol 3-kinase (PI3K) inhibitors as cancer therapeutics
... dysregulated PI3K pathway signaling has been implicated in conferring resistance to conventional therapies including biologics, hormonal therapy, tyrosine kinase inhibitors, radiation, and cytotoxics in ...
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PI3K inhibitors as new cancer therapeutics: implications for clinical trial design
... The PI3K–AKT–mTOR pathway is frequently activated in cancer. PI3K inhibitors, including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3Kα-selective inhibitor alpelisib (BYL719), ...
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Combination effects of sorafenib with PI3K inhibitors under hypoxia in colorectal cancer
... Results: In the 48-hour proliferation assay, sorafenib acted synergistically with GDC-0941 but not with BEZ-235. In long-term colony-forming assays, both GDC-0941 and BEZ-235 were shown to potentiate the ...
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Opposite regulation by PI3K/Akt and MAPK/ERK pathways of tissue factor expression, cell-associated procoagulant activity and invasiveness in MDA-MB-231 cells
... that PI3K inhibitors LY294002, wortmannin and A6730 significantly inhibited TF promoter activity, and reduced TF mRNA and protein levels due to the inhibition of Akt ...The PI3K/Akt pathway was shown ...
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RSK3/4 mediate resistance to PI3K pathway inhibitors in breast cancer
... of PI3K and RSK diminished rpS6 phosphorylation levels and proliferation compared with either inhibitor alone in breast can- cer cell lines with high levels of RSK (Figure 5C and Supplemen- tal Figure ...of ...
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PubMedCentral-PMC4816652.pdf
... ERK inhibitors will certainly require long-term treatment, the induction of this phenotype may be the more clinically relevant mechanism of ...the PI3K-AKT-mTOR pathway as a key mediator of ERK inhibitor ...
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Pi3k Signaling Pathway and Pten in Triple Negative Breast Cancer
... another PI3K inhibitor which is more advanced in clinical ...I PI3K, which equally inhibits class IA PI3Ks, but has no activity against class III PI3Ks or ...of PI3K pathway activation with both ...
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Opportunities and Resistance to Signal-Targeted Therapies in Pancreatic Cancer: What Can we Learn from Proteomic Studies?
... mTORC inhibitors have been identified using proteomics, explaining the disappointing results of the clinical trials on this target [38, 39, ...target PI3K/AKT/mTOR pathway, which is hyperactivated in 50% of ...
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The anti-tumor efficacy of CDK4/6 inhibition is enhanced by the combination with PI3K/AKT/mTOR inhibitors through impairment of glucose metabolism in TNBC cells
... with PI3K in- hibitors the synergism was lost, resulting in an additive inhibition of cell proliferation (Additional file 2: Figure ...the PI3K inhibitors ...the PI3K/AKT/mTOR path- way, as ...
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Genomic heterogeneity and efficacy of PI3K pathway inhibitors in patients with gynaecological cancer
... four patients with KRAS mutations who were treated with single-agent PAMi, none derived clinical benefit. Addi- tionally, we explored the impact of clonality of PIK3CA mutations on PAMi efficacy. PIK3CA clonal events, ...
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Hyperglycemia and Phosphatidylinositol 3-Kinase/Protein Kinase B/Mammalian Target of Rapamycin (PI3K/AKT/mTOR) Inhibitors in Phase I Trials: Incidence, Predictive Factors, and Management.
... using PI3K inhibitors have not reported dramatic hyperglycemia, an effect that may be related to the p110 isoform of the PI3K that is inhibited: a pan class 1A inhibitor may lead to more severe ...
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Will PI3K pathway inhibitors be effective as single agents in patients with cancer?
... TORC1/2 inhibitors, Chandarlapaty and colleagues showed that blockade of AKT (upstream of TORC1 and downstream of TORC2) with an allosteric kinase inhibitor also resulted in enhanced transcription and ...
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High-Throughput Phenotypic Screening of Kinase Inhibitors to Identify Drug Targets for Polycystic Kidney Disease
... few PI3K inhibitors that were effective at inhibiting cyst growth may also have activity against mTOR ...dual PI3K/mTOR inhibitors tested showed potent inhibition of forskolin-induced cyst ...
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Pharmacologic targeting of the PI3K/mTOR pathway controls release of angioregulators from primary human acute myeloid leukemia cells and their neighboring stromal cells
... mTOR inhibitors rapamycin and temsirolimus showed similarities in their inhibitory profile with a strong reduction of CXCL10, HGF and MMP-9 levels corresponding to p-values ...The PI3K-class III inhibitor ...
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Hypothalamic PI3K and MAPK differentially mediate regional sympathetic activation to insulin
... Because PI3K and MAPK are central molecules for many cellu- lar effects, we questioned the specificity of blockade of insulin- induced sympathoactivation by inhibition of these ...of PI3K and MAPK in the ...
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Prolonged inhibition of class I PI3K promotes liver cancer stem cell expansion by augmenting SGK3/GSK-3β/β-catenin signalling
... prolonged PI3K inhibitor treatment from enhancing CD133 expression in both Huh7 and MHCC97H ...the PI3K signalling pathway is a complex regulatory net- work, other downstream signal molecules may play a ...
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Dual inhibition of Type I and Type III PI3 kinases increases tumor cell apoptosis in HER2+ breast cancers
... I PI3K pathway blockade as a stop gap survival ...III PI3K inhibitors (like the Vps34 inhibitor) may enhance tumor cell killing in response to type I PI3K pathway ...
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The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations.
... diverse isoform-selectivity profiles in early to late clinical trial testing have unfortunately failed to live up to its promise with only very modest single agent activity. This has raised questions about how critical ...
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Blocking downstream signaling pathways in the context of HDAC inhibition promotes apoptosis preferentially in cells harboring mutant Ras
... the PI3K and MAPK pathways are the most studied and compounds targeting these pathways are in clinical development ...by inhibitors or AKT1 knockdown sensitized a series of colorectal cancers to the class I ...
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Computational drugs repositioning identifies inhibitors of oncogenic PI3K/AKT/P70S6K-dependent pathways among FDA- approved compounds
... well-known inhibitors of p110α catalytic subunit of ...of PI3K [28] (Table ...pump inhibitors are predicted to negatively regulate PI3K-dependent signalling ...inhibit PI3K-dependent ...
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