- |||||||||| Xalkori (crizotinib) / Pfizer
Journal: Amplification of wild type KRAS imparts resistance to crizotinib in MET exon 14 mutant non-small cell lung cancer. (Pubmed Central) - Nov 21, 2019 These results identify TFE3/IRS-1/PI3K/AKT/mTOR as a potential dysregulated pathway in TFE3-tRCC, and suggest a therapeutic potential of vertical inhibition of this axis by using a dual PI3K/mTOR inhibitor for TFE3-tRCC patients. Using patient-derived cell line and xenografts, we characterize the mechanism of crizotinib resistance mediated by KRAS amplification in METex14 mutant NSCLC and demonstrate the superior efficacy of the dual MET/PI3K inhibition as a therapeutic strategy addressing this resistance mechanism.
- |||||||||| Piqray (alpelisib) / Novartis
Biomarker, Journal: ERK-TSC2 signalling in constitutively-active HRAS mutant HNSCC cells promotes resistance to PI3K inhibition. (Pubmed Central) - Nov 21, 2019 HRAS mutant cells are resistant to PI3K inhibition and our findings suggest the involvement of a signalling intersection of the MAPK and PI3K pathways at the level of ERK-TSC2, leading to persistent mTOR activity. mTOR inhibition alone or in combination with MAPK pathway inhibition may be a promising therapeutic strategy for this subset of HNSCC tumors.
- |||||||||| Journal: miR-3666 inhibits lung cancer cell proliferation, migration and invasion by targeting BPTF. (Pubmed Central) - Nov 21, 2019
Finally, PI3K/AKT and EMT was demonstrated to be inhibited by miR-3666 overexpression in lung cancer cells. In conclusion, our data indicate that miR-3666 might play an essential role in cell proliferation, migration and invasion by targeting BPTF and partly inhibited PI3K/AKT and EMT signaling pathways in human lung cancers.
- |||||||||| cisplatin / Generic Mfg.
Journal: MALAT1 promotes cisplatin resistance in cervical cancer by activating the PI3K/AKT pathway. (Pubmed Central) - Nov 21, 2019 In conclusion, our data indicate that miR-3666 might play an essential role in cell proliferation, migration and invasion by targeting BPTF and partly inhibited PI3K/AKT and EMT signaling pathways in human lung cancers. MALAT1 promoted the cisplatin resistance of cervical cancer, which might be related to regulation of cell apoptosis via BRWD1 and PI3K/AKT pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly, endurobol (GW501516) / Ligand, GSK
Journal: Ligand-activated PPARδ inhibits angiotensin II-stimulated hypertrophy of vascular smooth muscle cells by targeting ROS. (Pubmed Central) - Nov 21, 2019 The phosphatidylinositol 3-kinase inhibitor LY294002 also inhibited Ang II-stimulated [3H]-leucine incorporation and ROS generation by preventing membrane translocation of Rac1. These observations suggest that PPARδ is an endogenous modulator of Ang II-triggered hypertrophy of VSMCs, and is thus a potential target to treat vascular diseases associated with hypertrophic changes of VSMCs.
- |||||||||| Journal, PARP Biomarker, IO Biomarker: Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma. (Pubmed Central) - Nov 21, 2019
Taken together, arnicolide D modulated the cell cycle, activated the caspase signaling pathway, and inhibited the PI3K/AKT/mTOR and STAT3 signaling pathways. These findings provide a solid base of evidence for arnicolide D as a lead compound for further development, and act as proof for the viability of drug development from traditional Chinese medicines.
- |||||||||| Journal: PIK3CA Double Mutations in Cis May Predict PI3Kα-Inhibitor Response. (Pubmed Central) - Nov 20, 2019
In conclusion, this study demonstrated that ghrelin pretreatment protected H9c2 cells against H/R-induced cell damage, possibly via PI3K/AKT and AMPK pathways. Cis double PIK3CA mutations are common in cancers and increase sensitivity to PI3Kα inhibitors.
- |||||||||| Trisenox (arsenic trioxide) / Teva, Medsenic
Preclinical, Journal: Arsenic induces autophagy in developmental mouse cerebral cortex and hippocampus by inhibiting PI3K/Akt/mTOR signaling pathway: involvement of blood-brain barrier's tight junction proteins. (Pubmed Central) - Nov 19, 2019 Here, the administration of arsenic trioxide (AsO) at doses of 0.15 mg or 1.5 mg or 15 mg AsO/L in drinking water from gestational to lactational and continued to the pups till PND42 resulted in a significant decrease in the mRNA expression levels of TJ proteins (Occludin, Claudin, ZO-1 and ZO-2) and Occludin protein expression level...The severities of changes were found to more persist in the cerebral cortex than in the hippocampus of As-exposed mice. Finally, we conclude that the leaky BBB in cerebral cortex and hippocampus may facilitate the transfer of As and induces autophagy by inhibiting PI3K/Akt/mTOR signaling pathway in an age-dependent manner, i.e., among the four different developmental age points, PND21 animals were found to be more vulnerable to the As-induced neurotoxicity than the other three age points.
- |||||||||| Journal: RIT1 suppresses esophageal squamous cell carcinoma growth and metastasis and predicts good prognosis. (Pubmed Central) - Nov 19, 2019
Our study also revealed that RIT1 increased drug sensitivity to cisplatin (CDDP), and this function could be carried out through downregulating stemness of ESCC. In conclusion, our study indicates for the first time that RIT1 displays tumor-suppressing functions in ESCC, and these functions were carried out by inhibiting MAPK and PI3K/AKT signaling pathway, inhibiting EMT, and downregulating cancer stemness of ESCC cells.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Azithromycin promotes alternatively activated macrophage phenotype in systematic lupus erythematosus via PI3K/Akt signaling pathway. (Pubmed Central) - Nov 19, 2019 After inhibiting Akt phosphorylation by LY294002, the down-regulation of CD80, IL-1β, IL-6, and TNF-α caused by azithromycin raised again, meanwhile, the up-regulation of CD206, Arg-1, Fizz-1, and IL-10 due to azithromycin was abolished...Taken together, our data indicated a novel role of azithromycin in alleviating SLE by promoting alternatively activated macrophage phenotype, and the PI3K/Akt signaling pathway was involved. Our findings provide a rationale for further investigation of novel therapeutic strategy for SLE patients.
- |||||||||| dactolisib (RTB101) / Novartis, PureTech
Journal: BMI1 Promotes Cardiac Fibrosis in Ischemia-Induced Heart Failure via the PTEN-PI3K/AKT-mTOR Signaling Pathway. (Pubmed Central) - Nov 19, 2019 At the same time, the effects of BMI1 on cardiac fibroblasts were reversed in vitro when these cells were exposed to NVP-BEZ235, a dual kinase (PI3K/mTOR) inhibitor. In conclusion, BMI1 is associated with cardiac fibrosis and dysfunction following MI by regulating cardiac fibroblast proliferation and migration, and these effects could be partially explained by the regulation of the PTEN-PI3K/AKT-mTOR pathway.
- |||||||||| Ibrance (palbociclib) / Pfizer, taselisib (GDC-0032) / Roche, pictilisib (GDC-0941) / Roche
Enrollment closed, Trial completion date, Combination therapy: PIPA: Combination of PI3 Kinase Inhibitors and PAlbociclib (clinicaltrials.gov) - Nov 19, 2019 P1, N=93, Active, not recruiting, The varied incidence of edema between therapeutic regimens warrants vigilant monitoring of patients treated with these therapies, especially those at high risk of developing BCRL. Recruiting --> Active, not recruiting | Trial completion date: Aug 2017 --> Jan 2020
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Deoxynivalenol-Induced Cytotoxicity and Apoptosis in IPEC-J2 Cells Through the Activation of Autophagy by Inhibiting PI3K-AKT-mTOR Signaling Pathway. (Pubmed Central) - Nov 18, 2019 With the purpose to explore the relationship between deoxynivalenol (DON)-induced apoptosis and autophagy and provide mechanistic explanations for the toxic effects of DON on IPEC-J2 cells, we determined the cell viability, cell morphology, apoptosis, and autophagy by using autophagy inhibitor 3-methyladenine (3-MA), PI3K pathway inhibitor LY294002, and activator 740Y-P...To conclude, these data reveal that DON may induce cytotoxicity and apoptosis through the activation of autophagy by suppressing the PI3K-AKT-mTOR signaling pathway. This study provides new insights into the mechanisms by which DON incurs cytotoxic effects.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Zydelig (idelalisib) / Gilead, Imbruvica (ibrutinib) / AbbVie, J&J
Review, Clinical Trial,Phase I, Clinical Trial,Phase II, Journal: From Biology to Therapy: The CLL Success Story. (Pubmed Central) - Nov 16, 2019 Further advances are achieved with venetoclax, a BH3-mimetic that specifically inhibits the antiapoptotic B-cell lymphoma 2 protein and thus causes rapid apoptosis of CLL cells, which translates into deep and prolonged clinical responses including high rates of minimal residual disease negativity. This review summarizes recent advances in the development of targeted CLL therapies, including new combination schemes, novel BTK and PI3K inhibitors, spleen tyrosine kinase inhibitors, immunomodulatory drugs, and cellular immunotherapy.
- |||||||||| Journal: MiR-4299 suppresses non-small cell lung cancer cell proliferation, migration and invasion through modulating PTEN/AKT/PI3K pathway. (Pubmed Central) - Nov 14, 2019
This review summarizes recent advances in the development of targeted CLL therapies, including new combination schemes, novel BTK and PI3K inhibitors, spleen tyrosine kinase inhibitors, immunomodulatory drugs, and cellular immunotherapy. We firstly indicated that miR-4299 may be a candidate independent marker for NSCLC prognosis and suppressed the progression of NSCLC by modulating the activation of PTEN/AKT/PI3K signaling pathway, suggesting that miR-4299 could be a potential target for developing therapies in treating NSCLC.
- |||||||||| Preclinical, Journal: MiRNA-26a promotes angiogenesis in a rat model of cerebral infarction via PI3K/AKT and MAPK/ERK pathway. (Pubmed Central) - Nov 14, 2019
We firstly indicated that miR-4299 may be a candidate independent marker for NSCLC prognosis and suppressed the progression of NSCLC by modulating the activation of PTEN/AKT/PI3K signaling pathway, suggesting that miR-4299 could be a potential target for developing therapies in treating NSCLC. MiRNA-26a promotes angiogenesis in a rat model of cerebral ischemic via PI3K/AKT and MAPK/ERK pathway.
- |||||||||| Journal: LncRNA NEAT1 regulates cervical carcinoma proliferation and invasion by targeting AKT/PI3K. (Pubmed Central) - Nov 14, 2019
LncRNA NEAT1 siRNA transfection can inhibit the proliferation of cervical cancer by regulating the AKT/PI3K signaling pathway, promote cell apoptosis, and restrain cell invasion. Therefore, the lncRNA NEAT1 may be used as a molecular potential for the diagnosis and treatment of cervical cancer through regulating AKT/PI3K signaling pathway, which would be confirmed in the following study.
- |||||||||| Journal: HOTTIP participates in mammary cancer by promoting cell proliferation via PI3K/AKT pathway. (Pubmed Central) - Nov 14, 2019
Therefore, the lncRNA NEAT1 may be used as a molecular potential for the diagnosis and treatment of cervical cancer through regulating AKT/PI3K signaling pathway, which would be confirmed in the following study. HOTTIP remarkably promotes proliferative and invasive abilities, but inhibits cell apoptosis of mammary cancer cells via PI3K/AKT pathway.
- |||||||||| Journal: Next-generation whole exome sequencing of glioblastoma with a primitive neuronal component. (Pubmed Central) - Nov 14, 2019
The next-generation sequencing can play a role in the diagnosis of GBM-PN especially for small biopsy cases. Eight out of 11 cases showed mutations in PTEN-PI3K pathway, which indicates that targeted therapeutic agents (PI3K inhibitors, mTORC1 inhibitors or dual PI3K/mTOR inhibitors) may be used for the treatment of GBM-PN in the future.
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