- |||||||||| Piqray (alpelisib) / Novartis, Tukysa (tucatinib) / Seagen
Clinical trial of Alpelisib and Tucatinib in patients with PIK3CA-mutant HER2-positive metastatic breast cancer (Hall 1) - Oct 28, 2022 - Abstract #SABCS2022SABCS_1934; P2 Clinically significant cardio-vascular disease Primary objectives: • Phase IB: safety and tolerability of combination therapy • Phase II: efficacy by progression free survival Exploratory assessment of biomarkers will be performed in the liquid biopsy samples. Study contact: Elena Shagisultanova, MD, PhD, elena.shagisultanova@cuanschutz.edu
- |||||||||| Journal: Computational Design of Phosphatidylinositol 3-Kinase Inhibitors. (Pubmed Central) - Oct 28, 2022
Compounds IV and XIV were found to be the most potent inhibitors of the human PI3K receptor with a high degree of stability within the active site of the target receptor for a timeframe of 50 ns. Thus, both of these compounds could be important drug candidates for the development of PI3K inhibitors as a prospective anticancer agent.
- |||||||||| 5-fluorouracil / Generic mfg.
Journal: SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer. (Pubmed Central) - Oct 27, 2022 In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment...Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy.
- |||||||||| lithium carbonate ER / Generic mfg., ketamine / Generic mfg.
Journal: Chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway. (Pubmed Central) - Oct 26, 2022 However, pharmacological inhibition of mammalian target of rapamycin (mTOR) signaling with rapamycin (10 mg/kg), a specific mTOR inhibitor, had no effect on ketamine-induced mania-like behavior. These results suggest that chronic lithium treatment ameliorates ketamine-induced mania-like behavior via the PI3K-AKT signaling pathway, which may be a novel target for the development of BD treatment.
- |||||||||| Audience Question and Answer Session (Elite B) - Oct 26, 2022 - Abstract #ASH2022ASH_494;
Supported by educational grants from AstraZeneca, BeiGene, Lilly, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC. Including MOA, key efficacy and safety data, and other considerations with BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors, and anti-CD20 mAbs
- |||||||||| On the horizon: MRD, CAR T-cell therapy, and other hot research areas (Elite B) - Oct 26, 2022 - Abstract #ASH2022ASH_493;
Supported by educational grants from AstraZeneca, BeiGene, Lilly, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC. Including MOA, key efficacy and safety data, and other considerations with BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors, and anti-CD20 mAbs
- |||||||||| Case discussions: putting it all together for effective management of CLL (Elite B) - Oct 26, 2022 - Abstract #ASH2022ASH_492;
Supported by educational grants from AstraZeneca, BeiGene, Lilly, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC. Including MOA, key efficacy and safety data, and other considerations with BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors, and anti-CD20 mAbs
- |||||||||| Mastering the current regimen components (Elite B) - Oct 26, 2022 - Abstract #ASH2022ASH_491;
Supported by educational grants from AstraZeneca, BeiGene, Lilly, and Pharmacyclics LLC, an AbbVie Company and Janssen Biotech, Inc., administered by Janssen Scientific Affairs, LLC. Including MOA, key efficacy and safety data, and other considerations with BTK inhibitors, BCL-2 inhibitors, PI3K inhibitors, and anti-CD20 mAbs
- |||||||||| ranolazine ER / Generic mfg.
Journal: Inhibition of late sodium current via PI3K/Akt signaling prevents cellular remodeling in tachypacing-induced HL-1 atrial myocytes. (Pubmed Central) - Oct 25, 2022 Those detrimental effects were related to increased I and were significantly mediated by treatment with the I blocker ranolazine. Furthermore, decreased PI3K/Akt signaling via PI3K inhibition increased I and subsequent aberrant myocyte excitability, which were abolished by I inhibition, suggesting that PI3K/Akt signaling is responsible for regulating pathogenic I. These results indicate that PI3K/Akt signaling is critical for regulating I and electrical remodeling, supporting the use of PI3K/Akt-mediated I as a therapeutic target for AF.
- |||||||||| samotolisib (LY3023414) / Eli Lilly, pictilisib (GDC-0941) / Roche, sapanisertib (CB-228) / Calithera
Journal: Anal Cancer Prevention Through the Topical Use of Single or Dual PI3K/mTOR Inhibitors. (Pubmed Central) - Oct 25, 2022 Sapanisertib, the mTOR inhibitor, had the greatest effect, in terms of increasing tumor-free survival, regardless of starting time point or sex. Unlike the other treatments, Samotolisib, the dual PI3K/mTOR inhibitor, decreased microscopic evidence of SqCC when starting treatment at 15 wk of age but only in male mice.
- |||||||||| pentylenetetrazole (BTD-001) / Balance Therap
Journal: Cannabidiol effect in pentylenetetrazole-induced seizures depends on PI3K. (Pubmed Central) - Oct 25, 2022 Our findings may contribute to the development of more effective therapies and may facilitate the prevention of drug resistance in FGFR1-positive cancer cells. Our data strengthen the hypothesis that the CBD anticonvulsant effect requires the PI3K signaling pathway.
- |||||||||| Journal: PI3K Isoforms in CD8 T Cell Development and Function. (Pubmed Central) - Oct 23, 2022
This chapter summarizes current knowledge of the roles of various PI3K isoforms and downstream signaling pathways in regulating CD8 T cell fate, including cell proliferation, migration, and memory generation. We also discuss certain clinical trials employing PI3K inhibitors for cancer therapy, their limitations, and future perspectives.
- |||||||||| Journal: The Role of PI3K Isoforms in Autoimmune Disease. (Pubmed Central) - Oct 23, 2022
Although progress has been hampered by issues such as poor drug tolerance and drug resistance, several PI3K inhibitors have now received regulatory approval with many others in development, including several intended to suppress the immune response in autoimmune and inflammatory diseases. This chapter reviews the evidence for contribution of aberrant PI3K activity to a range of autoimmune diseases (rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and type I diabetes) and possible therapeutic application of isoform-specific PI3K inhibitors as immunosuppressive drugs.
- |||||||||| Journal: PI3K Isoform Immunotherapy for Solid Tumours. (Pubmed Central) - Oct 23, 2022
Furthermore, we review how combination immunotherapy approaches with both PI3K inhibitors and subsequent immune checkpoint blockade can potentiate the efficacy of monotherapy. Finally, we discuss the recent advances in the use of PI3K isoform-specific inhibitors as an immunotherapy for solid tumours in clinical trials.
- |||||||||| Journal: PI3K Targeting in Non-solid Cancer. (Pubmed Central) - Oct 23, 2022
However, PI3K inhibition has yet to be approved for clinical use in ALL. Here, we review the role of PI3K signaling for normal hematopoietic and leukemia cells and summarize preclinical inhibitors of PI3K in ALL.
- |||||||||| Journal: Developing PI3K Inhibitors for Respiratory Diseases. (Pubmed Central) - Oct 23, 2022
In general, few clinical trials investigating PI3K inhibitors in respiratory disorders have been performed so far. This relatively new approach of treatment is just at its beginning and certainly needs further efforts and additional studies.
- |||||||||| Review, Journal: The role of PI3K/Akt signalling pathway in spinal cord injury. (Pubmed Central) - Oct 23, 2022
This review highlights the role of activating or inhibiting the PI3K/Akt signaling pathway in SCI-induced inflammatory response, apoptosis, autophagy, and glial scar formation. We also summarize the latest evidence on treating SCI by targeting the PI3K/Akt pathway, discuss the shortcomings and deficiencies of PI3K/Akt research in the field of SCI, and identify potential challenges in developing these clinical therapeutic SCI strategies, and provide appropriate solutions.
- |||||||||| cisplatin / Generic mfg.
Journal: Natural prenylated xanthones as potential inhibitors of PI3k/Akt/mTOR pathway in triple negative breast cancer cells. (Pubmed Central) - Oct 22, 2022 To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1: - 3: were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells...Furthermore, compound 2 significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.
- |||||||||| Journal: Urolithin A attenuates the severity of chronic pancreatitis associated with continued alcohol intake by inhibiting PI3K/AKT/mTOR signaling. (Pubmed Central) - Oct 22, 2022
Mice treated with Urolithin A (Uro A, a gut-derived microbial metabolite) in the setting of ACP with continued alcohol intake (during the recovery period) showed suppression of AKT and P70S6K activation, and acinar damage was significantly reduced with a parallel reduction in pancreas-infiltrating macrophages and pro-inflammatory cytokine accumulation. These results collectively provide mechanistic insight into the impact of Uro A on attenuation of ACP severity through suppression of PI3K/AKT/mTOR signaling pathways and can be a useful therapeutic approach in ACP patients with continuous alcohol intake.
- |||||||||| LY294002 / Eli Lilly
Journal: Stage-Dependent Activity and Pro-Chondrogenic Function of PI3K/AKT during Cartilage Neogenesis from Mesenchymal Stromal Cells. (Pubmed Central) - Oct 22, 2022 The effects of PI3K inhibition with LY294002 on chondrogenesis and hypertrophy were assessed via histology, qPCR, the quantification of proteoglycans, and alkaline phosphatase activity...Proving important for TGFβ-induced SMAD2 phosphorylation and SOX9 accumulation, PI3K/AKT activity was here identified as a required stage-dependent driver of chondrogenic speed but not of hypertrophy. Thus, future attempts to improve MSC chondrogenesis will depend on the adequate stimulation and upregulation of PI3K/AKT activity to generate high-quality cartilage from human MSCs.
- |||||||||| Review, Journal: Mitofusin-2 in cancer: Friend or foe? (Pubmed Central) - Oct 21, 2022
While remarkable progress has been achieved in recent decades, further exploration is required to elucidate whether MFN2 could be a friend or it's an enemy. This study aimed to highlight the different functions of MFN2 in various cancers.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, fimepinostat (CUDC-907) / Curis
Journal: Co-targeting of HDAC, PI3K, and Bcl-2 Results in Metabolic and Transcriptional Reprogramming and Decreased Mitochondrial Function in Acute Myeloid Leukemia. (Pubmed Central) - Oct 21, 2022 Our lab has previously demonstrated the promising outlook for CUDC-907, a dual inhibitor of PI3K and HDAC, in combination with venetoclax (VEN), against AML both in vitro and in vivo at least partially through suppression of c-Myc...CUDC-907 synergized with VEN in inducing apoptosis in the AraC-resistant AML cells. In conclusion, the CUDC-907 and VEN combination induces metabolic and transcriptomic reprograming and sup-pression of OXPHOS in AML, which provides additional mechanisms underlying the synergy between the two agents.
- |||||||||| NSC348884 / Targeted Cancer Therap, Zydelig (idelalisib) / Gilead
Journal: Discovery of Novel PI3Kδ Inhibitors Based on the p110δ Crystal Structure. (Pubmed Central) - Oct 21, 2022 Recently, we carried out virtual screening, cell-based assays, adapta kinase assays, and molecular dynamic analysis to discover novel PI3Kδ inhibitors and identified NSC348884 as a lead PI3Kδ inhibitor...In addition, we found that N, N, N-trimethyl-N-((6-methyl-1H-benzo[d]imidazol-2-yl) methyl) ethane-1,2-diamine might be a potential scaffold structure. Thus, the result of this study provides a far more efficient approach for discovering novel inhibitors targeting PI3Kδ.
- |||||||||| LY294002 / Eli Lilly
Review, Journal, IO biomarker: N-acetylserotonin protects PC12 cells from hydrogen peroxide induced damage through ROS mediated PI3K / AKT pathway. (Pubmed Central) - Oct 20, 2022 Moreover, NAS promoted the protein expression of p-PI3K and p-AKT, and the addition of the PI3K inhibitor LY294002 partially attenuated the antioxidant stress and anti-apoptotic effects of NAS in HO stimulated PC12 cells. In conclusion, NAS protected PC12 cells from apoptosis and oxidative stress induced by HO by inhibiting ROS activity and activating the PI3K/AKT signaling pathway.
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