- |||||||||| taselisib (GDC-0032) / Roche, AZD8186 / AstraZeneca, serabelisib (MLN1117) / Takeda, Petra Pharma, Faeth Therap
Journal: Recent Advances of PI3 Kinase Inhibitors: Structure Anticancer Activity Relationship Studies. (Pubmed Central) - Sep 20, 2022 The PI3K inhibitors which are under clinical trial studies include GDC-0032, INK1117 for PI3K-α, and AZD8186 for PI3K-β. This review primarily focuses on the structural insights and structure anticancer activity relationship studies of recent PI3K inhibitors including their clinical stages of development and therapeutic values.
- |||||||||| Piqray (alpelisib) / Novartis, Keytruda (pembrolizumab) / Merck (MSD), Jemperli (dostarlimab) / GSK
Biomarker, Clinical, Journal, Tumor Mutational Burden, BRCA Biomarker, MSi-H Biomarker, PARP Biomarker, PD(L)-1 Biomarker, IO biomarker: Biomarkers for Systemic Therapy in Metastatic Breast Cancer: ASCO Guideline Update. (Pubmed Central) - Sep 20, 2022 There are insufficient data to recommend routine testing of tumors for ESR1 mutations, for homologous recombination deficiency, or for TROP2 expression to guide MBC therapy selection. There are insufficient data to recommend routine use of ctDNA or circulating tumor cells to monitor response to therapy among patients with MBC.Additional information can be found at www.asco.org/breast-cancer-guidelines.
- |||||||||| Monjuvi (tafasitamab-cxix) / Incyte, parsaclisib (INCB50465) / Incyte
Enrollment open, Enrollment change, Combination therapy, Pan tumor: topMIND: A Study Evaluating Safety, PK, and Efficacy of Tafasitamab and Parsaclisib in Participants With Relapsed/Refractory Non Hodgkin Lymphoma (R/R NHL) or Chronic Lymphocytic Leukemia (CLL) (clinicaltrials.gov) - Sep 19, 2022 P1b/2a, N=100, Recruiting, Collectively, our findings revealed that exosomal miR-506 sensitized LUAD cells to CDDP-based HT by inhibiting ATAD2/PI3K/AKT signaling pathway, offering a potential therapeutic target for LUAD treatment. Active, not recruiting --> Recruiting | N=50 --> 100
- |||||||||| PI-103 / Roche, Zydelig (idelalisib) / Gilead, dactolisib (RTB101) / Adicet Bio
Journal: mTORC2 Is the Major Second Layer Kinase Negatively Regulating FOXO3 Activity. (Pubmed Central) - Sep 18, 2022 Furthermore, specific inhibition of mTOR kinase activity affecting both mTORC1 and mTORC2 potently induced nuclear translocation of FOXO3, while rapamycin, which specifically inhibits the mTORC1, failed to affect FOXO3...We also measured the effect of the test compounds on the phosphorylation status of AKT, FOXO3 and ERK, on FOXO-dependent transcriptional activity and on the subcellular localization of other FOXO isoforms. We conclude that mTORC2 is the most important second layer kinase negatively regulating FOXO activity.
- |||||||||| LY294002 / Eli Lilly
Journal: Sulforaphane Regulates eNOS Activation and NO Production via Src-Mediated PI3K/Akt Signaling in Human Endothelial EA.hy926 Cells. (Pubmed Central) - Sep 18, 2022 Meanwhile, pretreatment with LY294002 (a specific PI3K inhibitor) suppresses the phosphorylation of eNOS and NO production...Overall, the present study uncovers a novel effect of SFN to stimulate eNOS activity in EA.hy926 cells by regulating NO bioavailability. These findings provide clear evidence that SFN regulates eNOS activity and NO bioavailability, suggesting a promising therapeutic candidate to prevent endothelial dysfunction, atherosclerosis and other cardiovascular diseases.
- |||||||||| Undisclosed CDK4/6 inhibitor / CS Group
Biomarker, Journal: High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER breast cancer. (Pubmed Central) - Sep 16, 2022 Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies.
- |||||||||| paclitaxel / Generic mfg.
Journal: Paclitaxel Regulates TRPA1 Function and Expression Through PKA and PKC. (Pubmed Central) - Sep 14, 2022 PTX-induced neuropathy involves TRPA1 activity through an increase in functional expression and is regulated by PKA and PKC signaling. These findings support the role of the TRPA1 channel in the mechanisms altered by PTX, which can be involved in the process that lead to chemotherapy-induced neuropathy.
- |||||||||| progesterone / Generic mfg.
Journal: mPRα and PR co-operate in progesterone inhibition of endothelial cell focal adhesion. (Pubmed Central) - Sep 14, 2022 Knockdown of receptor expression with siRNA confirmed that mPRα mediates short-term and nPR long-term inhibitory effects of progesterone on FA signaling. Thus, progesterone inhibition of FA signaling and pre-atherosclerosis is coordinated through mPRα and nPRs.
- |||||||||| Journal: G protein-coupled receptor 30 mediates cell proliferation of goat mammary epithelial cells via MEK/ERK&PI3K/AKT signaling pathway. (Pubmed Central) - Sep 12, 2022
Importantly, MEK inhibitor and PI3K inhibitor decreased the expression of cell cycle regulators, and repressed estrogen-induced and G1-driven promotion of cell proliferation, suggesting that estrogen regulated cell proliferation of gMECs through mechanisms involving cell cycle, dependent of GPR30 and MEK/ERK and PI3K/AKT signaling pathway. This may provide a strong theoretical basis for researching estrogen sustained-release drugs promoting breast development and improving lactation performance.Abbreviations: gMECs, goat mammary epithelial cells; E2, 17β-estradiol; GPR30, G protein-coupled receptor 30; shRNA, small hairpin RNA; CDK, cyclin-dependent kinase; PI3K, phosphatidylinositol 3-kinase; AKT, proteinkinase B; MAPK, mitogen-activated protein kinase; MEK, mitogen-activated protein kinase kinase; ERK1/2, extracellular signal-regulated kinase 1/2.
- |||||||||| Journal: MiR-4268 suppresses gastric cancer genesis through inhibiting keratin 80. (Pubmed Central) - Sep 12, 2022
Finally, miR-4268 may function as tumor suppressor through inhibiting PI3K/AKT/JNK pathways by targeting KRT80 in GC. Collectively, our present results indicate that the miR-4268/KRT80 axis acts as a potential therapeutic target for patients with GC.AbbreviationsGastric cancer (GC); MicroRNAs (miRNAs); Keratin 80 (KRT80); differentially expressed genes (DEGs); chemoradiotherapy (CRT); negative nonsense sequence (NC); radioimmunoprecipitation assay (RIPA); polyvinylidene fluoride (PVDF).
- |||||||||| PIK-75 / VetDC
Journal: Targeting dual oncogenic machineries driven by TAL1 and PI3K-AKT pathways in Tcell acute lymphoblastic leukemia. (Pubmed Central) - Sep 11, 2022 TAL1-positive, AKT-activated T-ALL cells were very sensitive to PIK-75, as evidenced by the growth inhibition and apoptosis induction, while T-ALL cells that exhibited activation of the JAK-STAT pathway were insensitive to this drug. Together, our study demonstrates a strategy targeting two types of core machineries mediated by oncogenic transcription factors and signaling pathways in T-ALL.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Ghrelin infusion into the basolateral amygdala suppresses CTA memory formation in rats via the PI3K/Akt/mTOR and PLC/PKC signaling pathways. (Pubmed Central) - Sep 10, 2022 We showed that preadministration of the PI3K inhibitor LY294002 abolished the repressive effect of ghrelin on CTA memory...Preadministration of rapamycin eliminated the repressive effect of ghrelin, while Gsk3 inhibitors failed to mimic ghrelin's effect...By means of whole-cell recordings from rat brain slices, we showed that bath application of ghrelin (200 nM) had no effect on basal synaptic transmission or synaptic plasticity of BLA pyramidal neurons. Together, this study reveals the mechanism underlying ghrelin-induced interference with CTA memory acquisition in rats, i.e., suppression of intrinsic excitability of BLA principal neurons via the PI3K/Akt/mTOR and PLC/PKC pathways.
- |||||||||| CC-115 / BMS
Journal: Inhibition of mTORC1/2 and DNA-PK via CC-115 Synergizes with Carboplatin and Paclitaxel in Lung Squamous Cell Carcinoma. (Pubmed Central) - Sep 10, 2022 Because PI3K pathway and DNA-PK inhibitors have shown toxicity in clinical trials, we assessed toxicity by examining weight and numerous organs in PRKDC-wild type mice, which demonstrated that the combination treatment does not exacerbate the clinically accepted side effects of standard-of care-chemotherapy. This preclinical study provides strong support for the further investigation of CC-115 plus chemotherapy in LUSC.
- |||||||||| Piqray (alpelisib) / Novartis
P2 data, Journal, Monotherapy: Alpelisib monotherapy for PI3K-altered, pre-treated advanced breast cancer: a phase 2 study. (Pubmed Central) - Sep 10, 2022 Decline in PI3K pathway mutant ctDNA levels from baseline to week 8 while on therapy was significantly associated with a partial response, clinical benefit and improved progression free-survival (HR 0.24 95% CI 0.083 - 0.67, P = 0.0065). Detection of ESR1 mutations at baseline in plasma was also associated with clinical benefit and improved progression free survival (HR 0.22 95% CI 0.078 - 0.60, P = 0.003).
- |||||||||| nortriptyline / Generic mfg.
Journal: Drug-repositioning indicates a way to conquest corticosteroid-insensitivity (Pubmed Central) - Sep 10, 2022 Calcium-channel blocker saves lung function in patients with asthma in long-term observation. DR promises us to find cheap and safe options to treat difficult asthma by inhibiting specific intracellular signaling pathways.
- |||||||||| Istodax (romidepsin) / Astellas, BMS
Journal: Synthetic Study on Bicyclic Depsipeptides Containing an Intramolecular Disulfide Bond (Pubmed Central) - Sep 10, 2022 Among them, FK228 (romidepsin) is approved for treating cutaneous T-cell lymphoma and peripheral T-cell lymphoma...Furthermore, the analogs showed phosphatidylinositol 3-kinase (PI3K) inhibitory activity. Structural optimization of the analogs as HDAC/PI3K dual inhibitors led to the identification of FK-A11 as the most potent analog.
- |||||||||| fingolimod / Generic mfg.
Journal: PP2A regulates metastasis and vasculogenic mimicry formation via PI3K/AKT/ZEB1 axis in non-small cell lung cancers. (Pubmed Central) - Sep 10, 2022 Activation of PP2A with FTY720 or Ad-PP2A reduced phosphorylated AKT and inhibited ZEB1 transcription, thereby further downregulating the expression of MMP-2, VE-cadherin, and VEGFR-2, whereas inhibition of PP2A with okadaic acid (OA) or Ad-dn-PP2A exerted the opposite effect...This study indicated that PP2A could regulate VM formation in NSCLC through the PI3K/AKT/ZEB1 axis. PP2A reactivation or combination with PI3K inhibitor might be a more effective treatment against advanced NSCLC by inhibiting VM formation.
- |||||||||| Piqray (alpelisib) / Novartis
Re-sensitizing cancer cells to Tumor Treating Fields (TTFields) through PI3K/AKT/mTOR pathway inhibition (Gardehalle I & II) - Sep 9, 2022 - Abstract #EANO2022EANO_443; The current research demonstrated that PI3K/AKT/mTOR signaling pathway activation was involved in the response to long-term application of TTFields, with increased phosphorylation of key proteins observed both in vitro and in vivo . Concomitant treatment with PI3K inhibitors and TTFields re-sensitized the cells to TTFields, as it alleviated TTFields-induced AKT activation.
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