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  • ||||||||||  Preclinical, Journal:  Slit2/Robo1 signaling is involved in angiogenesis of glomerular endothelial cells exposed to a diabetic-like environment. (Pubmed Central) -  Oct 27, 2019   
    The effects induced by Slit2 were also abolished by Robo1 siRNA and PI3K inhibitor. Taken together, our findings indicate that in a diabetic-like environment, in addition to mesangial cells, autocrine activation of Slit2/Robo1 signaling of HRGECs may contribute to angiogenesis of HRGECs through PI3K/Akt/VEGF pathway; therefore, Slit2/Robo1 signaling may be a potent therapeutic target for the treatment of abnormal angiogenesis in early DN and may have broad implications for the treatment of other diseases dependent on pathologic angiogenesis.
  • ||||||||||  doxorubicin hydrochloride / generics
    Journal, IO Biomarker:  Drug-based perturbation screen uncovers synergistic drug combinations in Burkitt lymphoma. (Pubmed Central) -  Oct 27, 2019   
    In the combination screen, including BET, BTK and PI3K inhibitors, we identified synergistic combinations of PI3K and BTK inhibition with drugs targeting Akt, mTOR, BET and doxorubicin...The strongest synergy was observed for the combination of the CDK 2/7/9 inhibitor SNS032 and OTX015. Our data provide a landscape of drug combination effects in BL and suggest that targeting CDK and BET could provide a novel vulnerability of BL.
  • ||||||||||  Nexavar (sorafenib) / Bayer, Amgen
    A systems network approach for differential responses of Cancer Cells toward PI3K isoform Inhibitors () -  Oct 25, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_723;    
    Our study demonstrates the importance of the isoform specific targeted effects of the PI3K inhibitors through comprehensive pathways analyses alone or in combination with Sorafenib. Functional networks (http//github.com/kubranarci/Isoform-spesific-PI3K-inhibitor-analysis) identified in this study can be further investigated for novel drug targets to be exploited in the treatment of primary liver cancer.
  • ||||||||||  Opdivo (nivolumab) / Ono Pharma, BMS
    PARP and PI3K inhibitor combination therapy eradicates c-MYC-driven murine prostate cancers via cGAS/STING pathway activation within tumor-associated macrophages (Board 151: Level 2 - Hall D) -  Oct 25, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_677;    
    Taken together, these results demonstrate that the DNA damage elicited by PARPi/PI3Ki can reprogram the myeloid tumor microenvironment (TME) to enhance anti-tumor immunity, resulting in effective tumor eradication in ICB-refractory cancers. Preliminary immune profiling of paired metastatic biopsies from a combination co-clinical trial in castrate-resistant prostate cancer patients, showed decreased immunosuppression and T cell activation within the TME following 4 weeks of treatment with rucaparib/nivolumab, thus supporting the preclinical data described above.
  • ||||||||||  LSD1 activates both PI3K/AKT and AR signaling in prostate cancer cells (Board 160: Level 2 - Hall D) -  Oct 25, 2019 - Abstract #AACRNCIEORTC2019AACR_NCI_EORTC_664;    
    Based on these findings, it is plausible that the effectiveness of LSD1 inhibitor treatment in CRPC may be due to inhibition of both AR signaling and PI3K/AKT signaling pathways. As LSD1 inhibitors are currently being tested in phase II clinical trials of leukemia, our studies can be rapidly translated into clinical trials of CRPC.
  • ||||||||||  Clinical, Journal:  PI3K/AKT/mTOR pathway in multiple myeloma: from basic biology to clinical promise. (Pubmed Central) -  Oct 24, 2019   
    The phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is such a pathway that is aberrantly activated in a large proportion of MM patients through numerous mechanisms and can play a role in resistance to several existing therapies making this a central pathway in MM pathophysiology. Here, we review the pathway, its role in MM, promising preclinical results obtained thus far and the clinical promise that drugs targeting this pathway have in MM.
  • ||||||||||  JQ-1 / Roche
    Biomarker, Journal:  EGFR-mediated signaling pathway influences the sensitivity of oral squamous cell carcinoma to JQ1. (Pubmed Central) -  Oct 24, 2019   
    In summary, our findings revealed that JQ1 can act by inhibiting the EGFR-mediated signaling pathway, and EGFR expression influences the sensitivity of OSCC to JQ1. Regarding clinical use, this study demonstrates that BRD4 is a novel therapeutic target and EGFR can be used as a biomarker to identify the most appropriate anti-BRD4 treatment strategy in OSCC.
  • ||||||||||  TriptoSar (triptolide) / Pierre Fabre
    Journal:  Triptolide induces autophagy of ovarian granulosa cells via PI3K/AKT/m TOR pathway (Pubmed Central) -  Oct 24, 2019   
    At the same time,TP could significantly inhibit the expression of p-PI3 K,p-AKT,p-mTOR protein,and the inhibitory effect of TP was better than that of NVP-BEZ235 group. This study suggests that 100 nmol·L-1 TP could induce OGCs autophagy successfully in cultured rat ovary for 12 h; TP may induce OGCs autophagy by inhibiting PI3 k/Akt/m TOR signaling pathway.
  • ||||||||||  Biomarker, Review, Journal:  Novel therapeutic avenues in triple-negative breast cancer: PI3K/AKT inhibition, androgen receptor blockade, and beyond. (Pubmed Central) -  Oct 23, 2019   
    In this context, the inhibition of phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and androgen receptor (AR) signaling pathways have emerged as potential therapeutic strategies against selected tumors. In this paper, we reviewed the preclinical rationale, predictive biomarkers, efficacy, and safety data from early phase trials, and the future directions for these two biomarker-directed treatment approaches in TNBC.
  • ||||||||||  Journal:  ReishiMax inhibits mTORC1/2 by activating AMPK and inhibiting IGFR/PI3K/Rheb in tumor cells. (Pubmed Central) -  Oct 23, 2019   
    Ectopic expression of dominant-negative AMPKα partially mitigated the inhibitory effect of GLPT on mTORC1, indicating that GLPT inhibits mTORC1 partly by activating AMPK. The results suggest that G. lucidum extracts exert anticancer action at least partly by suppressing mTORC1/2 signaling via activation of AMPK and inhibition of IGFR/PI3K/Rheb in tumor cells.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  SERPIND1 Affects the Malignant Biological Behavior of Epithelial Ovarian Cancer via the PI3K/AKT Pathway: A Mechanistic Study. (Pubmed Central) -  Oct 23, 2019   
    The addition of the PI3K/AKT pathway inhibitor LY294002 to SERPIND1-overexpressing cells could reverse the promoting effect of SERPIND1 on the malignant biological behavior of ovarian cancer cells...In conclusion, our results indicated that SERPIND1 could be an effective marker for assessing the prognosis of ovarian cancer. By elucidating its mechanism underlying the promotion of malignant biological behavior of ovarian cancer by SERPIND1, we demonstrated that SERPIND1 could potentially serve as a novel drug target.
  • ||||||||||  fuzheng Huayu / Shanghai Sundise
    Journal:  Yu Jin Pulvis inhibits carbon tetrachloride-induced liver fibrosis by blocking the MAPK and PI3K/Akt signaling pathways. (Pubmed Central) -  Oct 22, 2019   
    Mice were randomly divided into normal, CCl, YJP (300 mg/kg), CCl+YJP (100, 200, and 300 mg/kg), and two positive control silybin (100 mg/kg) and Fuzheng Huayu (FZHY) capsule (2 g/kg) groups...Collectively, these results demonstrate the antifibrosis effect of YJP on CCl-induced liver fibrosis in mice, mediated through blockade of the MAPK and PI3K/Akt signaling pathways. Therefore, YJP has therapeutic potential against liver fibrosis.
  • ||||||||||  quercetin (LY294002) / Eli Lilly
    Journal:  Hepatitis B spliced protein (HBSP) suppresses Fas-mediated hepatocyte apoptosis via activation of PI3K/Akt signaling. (Pubmed Central) -  Oct 20, 2019   
    Confirmedly, inhibition of PI3K by LY294002 reversed the effect of HBSP on Fas aggregation, FLIP expression, and cellular apoptosis...In particular, HBV variants associated with hepatoma carcinoma may down-regulate apoptosis of hepatocytes through enhanced HBSP expression. Our study also found that AKT is centrally involved in Fas-induced hepatocyte apoptosis and revealed interventions directed at inhibiting the activation or functional activity of AKT may be of therapeutic value in this process.
  • ||||||||||  Kyprolis (carfilzomib) / Amgen, Ono Pharma
    Preclinical, Journal:  Molecular mechanisms of Carfilzomib-induced cardiotoxicity in mice and the emerging cardioprotective role of Metformin. (Pubmed Central) -  Oct 20, 2019   
    Co-administration of Met prevented Cfz-induced FS reduction and restored AMPKα phosphorylation and autophagic signaling. Conclusively, Cfz decreased left ventricular function through increased PP2A activity and inhibition of AMPKα and its downstream autophagic targets, while Met represents a novel promising intervention against Cfz-induced cardiotoxicity.