- |||||||||| Clinical, Preclinical, Journal: WWP1 inactivation enhances efficacy of PI3K inhibitors while suppressing their toxicities in breast cancer models. (Pubmed Central) - Jan 7, 2022
Mechanistically, we found that AMPKα2 was ubiquitinated and, in turn, inhibited in its activatory phosphorylation by WWP1, whereas WWP1 inhibition facilitated AMPKα2 activity in the muscle to compensate for the reduction in glucose uptake observed upon PI3K inhibition. Thus, our identification of the cell-autonomous and systemic roles of WWP1 inhibition expands the therapeutic potential of PI3K inhibitors and reveals new avenues of combination cancer therapy.
- |||||||||| Biomarker, Journal: Can Improved Use of Biomarkers Alter the Fate of PI3K Pathway Inhibitors in the Clinic? (Pubmed Central) - Jan 7, 2022
Although many potent and selective inhibitors have been developed and evaluated in preclinical models, their progress to clinical approval has been limited. Here we discuss the pressing need to develop improved biomarker strategies to guide patient selection and improve assessment of patient responses to PI3K pathway inhibitors to address unresolved issues surrounding the efficacy and tolerability of these compounds in patients with cancer.
- |||||||||| paclitaxel / Generic mfg.
Journal: Tenascin C Promotes Glioma Cell Malignant Behavior and Inhibits Chemosensitivity to Paclitaxel via Activation of the PI3K/AKT Signaling Pathway. (Pubmed Central) - Jan 6, 2022 In terms of stemness, TNC increased the sphere number per 1000 cells, CD44CD133 cell percentage and 1/stem cell frequency (assessed by extreme limiting dilution analysis) in U251 cells. In rescue experiments, 740 Y-P reduced the effect of TNC on proliferation, apoptosis, chemosensitivity to paclitaxel, and stemness in U251 cells. TNC acts as an oncogenic factor by promoting cancer cell proliferation and stemness while inhibiting apoptosis and chemosensitivity to paclitaxel in glioma via modulation of PI3K/AKT signaling.
- |||||||||| CYH33 / HaiHe Biopharma
Preclinical, Journal: PI3Kα inhibitor CYH33 triggers antitumor immunity in murine breast cancer by activating CD8T cells and promoting fatty acid metabolism. (Pubmed Central) - Jan 6, 2022 A combined treatment of curcumin and probucol could be used to protect chondrocytes from inflammatory cytokine stress via inhibition of the autophagy-related PI3K/Akt/mTOR pathway both in vitro and in vivo, which might be of potential pharmaceutical value for OA prevention and therapy. CYH33 induces immune activation and synergizes with FASN inhibitor to further promote the antitumor immunity, which gains novel insights into how PI3K inhibitors exert their activity by modulating TME and provides a rationale for the concurrent targeting of PI3K and FASN in breast cancer treatment.
- |||||||||| Journal: Dominant Role of PI3K p110α over p110β in Insulin and β-Adrenergic Receptor Signalling. (Pubmed Central) - Jan 6, 2022
We also demonstrate that p110α is the principal isoform activated downstream of the β-adrenergic receptor (β-AR), another important signalling pathway in metabolic regulation, through a mechanism involving activation of the cAMP effector molecule EPAC1. This study offers further insights in the role of PI3K isoforms in the regulation of energy metabolism with implications for the therapeutic application of selective inhibitors of these isoforms.
- |||||||||| Halaven (eribulin mesylate) / Eisai, Aliqopa (copanlisib) / Bayer
Trial completion date, Trial primary completion date, Combination therapy, Metastases: Testing the Addition of Copanlisib to Eribulin for the Treatment of Advanced-Stage Triple Negative Breast Cancer (clinicaltrials.gov) - Jan 6, 2022 P1/2, N=18, Recruiting, This study offers further insights in the role of PI3K isoforms in the regulation of energy metabolism with implications for the therapeutic application of selective inhibitors of these isoforms. Trial completion date: Dec 2021 --> Dec 2022 | Trial primary completion date: Dec 2021 --> Dec 2022
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: Akt and its phosphorylation in nucleus accumbens mediate heroin-seeking behavior induced by cues in rats. (Pubmed Central) - Jan 5, 2022 Akt is initially identified as one of the downstream targets of phosphatidylinositol-3 kinase (PI3K) and is involved in morphine reward and tolerance...Additionally, a microinjection of LY294002, an inhibitor of PI3K, into the NAc inhibited the CS-induced heroin-seeking behaviors after 14 days of withdrawal, paralleling the decreased levels of p-Akt in the NAc...CS-induced heroin-seeking behavior was inhibited by downregulation of Akt1, but not β-arrestin 2, in the NAc. These data demonstrate that Akt phosphorylation in the NAc may play an important role in the incubation of heroin-seeking behavior, suggesting that the PI3K/Akt pathways may be involved in the process of heroin relapse and addiction.
- |||||||||| Journal: Discovery of Cinnoline Derivatives as Potent PI3K Inhibitors with Antiproliferative Activity. (Pubmed Central) - Jan 5, 2022
In this study, a series of cinnoline derivatives were developed as PI3K inhibitors and evaluated for enzymatic and cellular activities. Most compounds displayed nanomolar inhibitory activities against PI3Ks, among which 25 displayed high LLE and micromolar inhibitory potency against three human tumor cell lines (IC = 0.264 μM, 2.04 μM, 1.14 μM).
- |||||||||| Review, Journal: PI3K in T Cell Adhesion and Trafficking. (Pubmed Central) - Jan 5, 2022
This review will focus on the regulation of adhesion receptors by PI3Kδ and how this contributes to T cell trafficking and localisation. These findings are relevant for our understanding of how PI3Kδ inhibitors may affect T cell redistribution and function.
- |||||||||| Review, Journal: PI3K signalling in chronic obstructive pulmonary disease and opportunities for therapy. (Pubmed Central) - Jan 4, 2022
In this review, we discuss the critically important roles played by hyper-activated PI3K signalling in the pathogenesis of COPD. We also critically review current therapeutics based on PI3K inhibition, and provide suggestions focusing on PI3K signalling for the further improvement of the COPD phenotype.
- |||||||||| Journal: CN-3 induces mitochondrial apoptosis in glioma via Ros-mediated PI3K/AKT pathway. (Pubmed Central) - Jan 4, 2022
Furthermore, we detected that CN-3 downregulated PI3K, P-Akt, AKT and BCL-2, and upregulated cytochrome C and BAX in U87 and U251 cells. Moreover, ROS triggered the inhibition and cell apoptosis for CN-3 via inactivation of P-Akt and activation of cytochrome C. In conclusion, these findings suggest that CN-3 may be a promising candidate for the development of a therapy of glioma.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: The oncogenic role of the cerebral endothelial cell adhesion molecule (CERCAM) in bladder cancer cells in vitro and in vivo. (Pubmed Central) - Jan 4, 2022 The PI3K inhibitor LY294002 treatment manifested similar effects as CERCAM silencing on bladder cancer cell behaviors and partially impaired the promotive functions of CERCAM overexpression upon the capacity of bladder cancer cells to proliferate and invade...In vitro, CERCAM overexpression significantly promoted bladder cancer cell viability, DNA synthesis, and cell invasion and alters the cleaved-caspase3, E-cadherin, and N-cadherin expression pattern; in vivo, CERCAM silencing suppressed tumor growth in nude mice. The PI3K/AKT signaling is suspected of interfering participate in the functions of CERCAM in bladder carcinoma.
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