PI3K inhib 
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  • ||||||||||  LY294002 / Eli Lilly, AG1478 / IDT Australia
    Journal:  Cryptosporidium parvum maintains intracellular survival by activating the host cellular EGFR-PI3K/Akt signaling pathway. (Pubmed Central) -  Jan 10, 2023   
    The EGFR inhibitor AG1478 decreased EGFR and Akt phosphorylation, and the PI3K inhibitor LY294002 impaired Akt phosphorylation induced by C. parvum in HCT-8 cells...Intracellular parasite proliferation was decreased when treated with autophagy inducer rapamycin, whereas autophagy inhibitor 3-MA, E64d+pep A, siBeclin1 or siATG7 increased intracellular parasites...In summary, C. parvum could maintain intracellular survival by inhibiting autophagy via EGFR-PI3K/Akt pathway. These results revealed a new mechanism for the interaction of C. parvum with host cells.
  • ||||||||||  tamoxifen / Generic mfg.
    Journal:  2D-CuPd nanozyme overcome tamoxifen resistance in breast cancer by regulating the PI3K/AKT/mTOR pathway. (Pubmed Central) -  Jan 10, 2023   
    Our results reveal a novel nanozyme ROS-mediated protein mechanism for the regulation of the PI3K subunit, illustrate the cellular pathways through which increased p85β protein expression contributes to tamoxifen resistance, and reveal p85β protein as a potential therapeutic target for overcoming tamoxifen resistance. 2D-CuPd is the first reported nanomaterial capable of degrading PI3K subunits, and its high performance combined with further materials engineering may lead to the development of nanozyme-based tumor catalytic therapy.
  • ||||||||||  Journal:  PI3K δ inhibitor PI-3065 induces apoptosis in hepatocellular carcinoma cells by targeting survivin. (Pubmed Central) -  Jan 10, 2023   
    Furthermore, transplantation of nude mice with HCC tumors showed that PI-3065 inhibits HCC tumor growth in vivo by targeting survivin. In summary, PI-3065 specifically inhibited survivin expression and exerted anti-HCC activity in vivo and in vitro, suggesting that it may serve as an effective antitumor drug for HCC treatment, which warrants further study.
  • ||||||||||  Journal:  On the Therapeutic Potential of ERK4 in Triple-Negative Breast Cancer. (Pubmed Central) -  Jan 9, 2023   
    They concluded that ERK4 is a promising therapeutic target for TNBC and has potential for combination therapy with PI3K inhibitors. Here, we raise concerns about the cellular models and experimental approaches used in this study, which compromise the conclusions on the oncogenic role of ERK4 in TNBC.
  • ||||||||||  Zanosar (streptozocin) / Teva
    Journal:  HO Mediates VEGF- and Flow-Induced Dilations of Coronary Arterioles in Early Type 1 Diabetes: Role of Vascular Arginase and PI3K-Linked eNOS Uncoupling. (Pubmed Central) -  Jan 9, 2023   
    This hypothesis was tested in coronary arterioles isolated from pigs with 2-week diabetes after streptozocin injection...This study demonstrates that endothelium-dependent NO-mediated coronary arteriolar dilation is partially compromised in early type 1 diabetes by reducing eNOS substrate L-arginine via arginase activation. It appears that upregulated arginase contributes to endothelial NO deficiency in early diabetes, but production of HO during PI3K-linked eNOS uncoupling likely compensates for and masks this disturbance.
  • ||||||||||  Herceptin (trastuzumab) / Roche, Itovebi (inavolisib) / Roche
    Enrollment open, Trial completion date, Trial initiation date, Trial primary completion date, Combination therapy:  GeparPiPPa: Neoadjuvant Endocrine Therapy +/- the PI3K Inhibitor Inavolisib in HER2+, HR+, PIK3CA Mutant Early Breast Cancer (clinicaltrials.gov) -  Jan 9, 2023   
    P2,  N=170, Recruiting, 
    Quercetin has a role in the treatment of UC, with pharmacological mechanisms that involve regulation of the intestinal microbiota, re-establishment of healthy microbiomes that favor mucosal healing, and the inhibition of PI3K/AKT signaling. Not yet recruiting --> Recruiting | Trial completion date: Jun 2026 --> Jan 2027 | Initiation date: Jun 2022 --> Jan 2023 | Trial primary completion date: Mar 2026 --> Oct 2026
  • ||||||||||  paclitaxel / Generic mfg.
    Journal:  Antitumor Effects of Ononin by Modulation of Apoptosis in Non-Small-Cell Lung Cancer through Inhibiting PI3K/Akt/mTOR Pathway. (Pubmed Central) -  Jan 7, 2023   
    Paclitaxel (PTX) is a commonly used chemotherapeutic drug for NSCLC, which can cause tissue injury in healthy cells and affect the quality of life in patients with cancer...Based on the histological analysis, the cotreatment of PTX and ononin reduced PTX-induced liver and kidney damage. Overall, our findings suggested that the therapeutic index of PTX-based chemotherapy could be improved by reducing toxicity with increasing antitumor capabilities when combined with ononin.
  • ||||||||||  Preclinical, Journal:  LDL-Dependent Regulation of TNFα/PGE Induced COX-2/mPGES-1 Expression in Human Macrophage Cell Lines. (Pubmed Central) -  Jan 5, 2023   
    LDL repressed basal ERK phosphorylation and expression of downstream transcription factor Egr-1, which might lead to inhibition of COX-2 expression. These findings suggest that simultaneous stimulation with a combination of TNFα, PGE, and native LDL-activated signal chains in macrophage cell lines leads to maximal mPGES-1 activity, as well repression of COX-2 expression, by activating PI3K as well as repression of ERK/Egr-1 signal chains.
  • ||||||||||  LY294002 / Eli Lilly
    Journal:  Transcriptional regulation of Notch1 by nuclear factor-κB during T cell activation. (Pubmed Central) -  Jan 3, 2023   
    Both the surface expression and mRNA transcription of Notch1 were significantly higher in activated CD4 T cells, but the inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 or deletion of the Pdk1 gene impaired this upregulation of Notch1...In addition, inhibition of NF-κB by SN50 impaired upregulation of Notch1 surface protein and mRNA in activated CD4 T cells. Thus, we provide evidence that Notch1 transcription in activated CD4 T cells is upregulated via the PI3K-PDK1-NF-κB signaling pathway.
  • ||||||||||  Journal:  Collective directional migration drives the formation of heteroclonal cancer cell clusters. (Pubmed Central) -  Jan 2, 2023   
    Such a hypothesis is consistent with the abrogation of aggregation by inhibition of PI3K/AKT/mTOR and MEK/ERK, the chemoattracting activity of conditioned culture media and with a wide screening on secreted proteins. Our results present a novel collective migration model and shed light on the mechanisms of formation of heteroclonal aggregates in cancer.
  • ||||||||||  Piqray (alpelisib) / Novartis
    Journal:  PIK3CAMutations in Breast Cancer Subtypes Other Than HR-Positive/HER2-Negative. (Pubmed Central) -  Dec 30, 2022   
    Among PI3Ki, alpelisib, a selective p110α inhibitor, is approved for the treatment of hormone receptor (HR)+/HER2- PIK3CA mutant metastatic breast cancer (BC) that has progressed to a first line endocrine therapy...In this review, we go through the PI3K/AKT/mTOR pathway, describing most common mutations found in PI3K genes and how they can be detected. We describe the available biological and clinical evidence of PIK3CA mutations in breast cancers other than HR+/HER2-, summarizing clinical trials investigating PI3Ki in these subtypes.
  • ||||||||||  Nested Stromal and Epithelial Tumor (NSET) of the Liver: Report of 2 Cases with PTEN Mutation (Exhibit Hall B; 61) -  Dec 29, 2022 - Abstract #USCAP2023USCAP_1873;    
    We report 2 cases of morphologically and immunohistochemically typical cases of NSET with PTEN mutation, representing a novel molecular event detected in this tumor type. As one case presented with both pathogenic PTEN mutation and CTNNB1 mutation it seems that CTNNB1 mutations might be accompanied not only by TERT promoter mutations but also co-occur with other alterations such as PTEN and in rare cases, they can be absent altogether.
  • ||||||||||  sirolimus / Generic mfg.
    Journal, IO biomarker:  HRK inhibits colorectal cancer cells proliferation by suppressing the PI3K/AKT/mTOR pathway. (Pubmed Central) -  Dec 27, 2022   
    In addition, rapamycin inhibits the activation of PI3K/AKT/mTOR signaling pathway and reverses HRK-induced alterations in cell biological functions...And for the first time, HRK was shown to promote apoptosis and inhibit proliferation of colorectal cancer cells by inhibiting PI3K/AKT/mTOR signaling pathway. HRK represents a potential target for the treatment of CRC.
  • ||||||||||  XAV-939 / Novartis
    Journal:  Limonin, a Component of Immature Citrus Fruits, Activates Anagen Signaling in Dermal Papilla Cells. (Pubmed Central) -  Dec 24, 2022   
    XAV939, a Wnt/β-catenin inhibitor, inhibited these limonin-induced changes, including induced autophagy, BrdU-positive cells, and cell proliferation...Wortmannin also inhibited limonin-induced cyclin D1 and LC3 expression in spheroids. Collectively, these results indicate that limonin can enhance anagen signaling by activating autophagy via targeting the Wnt/β-catenin and/or PI3K/AKT pathways in rDPC, highlighting a candidate nutrient for hair loss treatment.