- |||||||||| everolimus / Generic mfg.
Review, Journal: Targeting the PI3K/Akt/mTOR pathway in estrogen-receptor positive HER2 negative advanced breast cancer. (Pubmed Central) - Aug 13, 2020 For the moment, the only positive trials showing a progression free survival benefit in this population are BOLERO-2 (2012), SOLAR-1 (2019), which tested everolimus, a mammalian target of rapamycin inhibitor, and alpelisib, a PI3K inhibitor, and led to their marketing authorization. However, many other inhibitors of this pathway are promising; nevertheless their development is actually limited by toxicity, mainly cutaneous (rash), digestive (diarrhea) and endocrine (diabetes).
- |||||||||| Istodax (romidepsin) / Astellas, BMS, Aliqopa (copanlisib) / Bayer
Enrollment change, Trial withdrawal, Combination therapy: Copanlisib in Combination With Romidepsin in Patients With Relapsed or Refractory Mature T-cell Lymphoma (clinicaltrials.gov) - Aug 12, 2020 P1b, N=0, Withdrawn, However, many other inhibitors of this pathway are promising; nevertheless their development is actually limited by toxicity, mainly cutaneous (rash), digestive (diarrhea) and endocrine (diabetes). N=30 --> 0 | Not yet recruiting --> Withdrawn
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal, IO Biomarker: Administration of rCTRP9 Attenuates Neuronal Apoptosis Through AdipoR1/PI3K/Akt Signaling Pathway after ICH in Mice. (Pubmed Central) - Aug 11, 2020 To elucidate the underlying mechanisms, adiponectin receptor1 small interfering ribonucleic acid (AdipoR1 siRNA) and selective PI3 K inhibitor LY294002 were administered prior to rCTRP9 treatment...Administration of rCTRP9 significantly improved both short- and long-term neurofunctional behavior after ICH. RCTRP9 treatment significantly increased the expression of AdipoR1, PI3 K, p-Akt, and Bcl-2, while at the same time was found to decrease the expression of Bax in the brain, which was reversed by inhibition of AdipoR1 and PI3 K. The neuroprotective effect of rCTRP9 after ICH was mediated by attenuation of neuronal apoptosis via the AdipoR1/PI3K/Akt signaling pathway; therefore, rCTRP9 should be further evaluated as a potential therapeutic agent for ICH patients.
- |||||||||| omipalisib (GSK2126458) / GSK
Clinical, Journal: A Randomised, Placebo-Controlled Study of Omipalisib (PI3K/mTOR) in Idiopathic Pulmonary Fibrosis. (Pubmed Central) - Aug 11, 2020 P1 Exposure dependent inhibition of PIP3 and pAKT confirmed target engagement in blood and lungs. [18F]-FDG-PET/CT scans revealed an exposure dependent reduction in [18F]-FDG uptake in fibrotic areas of the lung, as measured by target to background ratio (TBR) thus confirming pharmacodynamic activity.This experimental medicine study demonstrates acceptable tolerability of omipalisib in subjects with IPF at exposures for which target engagement was confirmed both systemically and in the lungs.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, BRCA Biomarker: The Interaction of PI3K Inhibition with Homologous Recombination Repair in Triple Negative Breast Cancer Cells. (Pubmed Central) - Aug 11, 2020 Together, our findings indicate that BDNF enhances T-type currents through the stimulation of TrkB coupled to PI3K-p38-PKA signaling, thereby inducing neuronal hyperexcitability of TG neurons and pain hypersensitivity in rats. Consequently, targeted therapies based on the interaction of PI3K inhibition with BRCA1 mutations or HR deficiency in TNBC may be a promising strategy for the treatment of patients with TNBC.
- |||||||||| Journal: Squalene epoxidase induced cholesteryl ester accumulation promotes NPC development through activating PI3K/AKT signaling. (Pubmed Central) - Aug 11, 2020
Mechanism study demonstrated that cholesteryl ester promoted NPC cells proliferation by activating PI3K/AKT pathway and inhibition of this pathway in SQLE over-expressed or cholesteryl ester treated cells resulted in a significant reduction of NPC cells proliferation. These results indicate that the oncogenic effect of SQLE in NPC mainly resulted from cholesteryl ester accumulation and PI3K/AKT is a promising target for NPC with SQLE over-expression.
- |||||||||| Clinical, Journal, IO Biomarker: miR-188-5p Promotes Tumor Growth by Targeting CD2AP Through PI3K/AKT/mTOR Signaling in Children with Acute Promyelocytic Leukemia. (Pubmed Central) - Aug 9, 2020
Rescue experiments showed that inhibition of miR-188-5p inhibited cell proliferation, activated the PI3K/AKT/mTOR signaling pathway, induced G0/G1 phase arrest, regulated gene expression, and promoted cell apoptosis, which were reversed by CD2AP inhibition. miR-188-5p, an oncogene, promoted tumor growth and progression of pediatric APL in vitro and in vivo via targeting CD2AP and activating the PI3K/AKT/mTOR signaling pathway.
- |||||||||| temozolomide / Generic mfg.
Journal: TRIM31 enhances chemoresistance in glioblastoma through activation of the PI3K/Akt signaling pathway. (Pubmed Central) - Aug 9, 2020 Temozolomide (TMZ) resistance is a complication of treatment of glioma, and new strategies are urgently required to overcome chemoresistance in glioma cells...Overexpression of TRIM31 increased phosphorylation of AKT and inhibiting the PI3K/AKT signaling pathway abolished the increase in cell viability and decreased phospho-Akt protein expression in TRIM31 overexpressing A172 cells treated with TMZ. Together, the findings suggest that TRIM31 may be a potentially novel target for glioma chemotherapy.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Trp53 regulates platelets in bone marrow via the PI3K pathway. (Pubmed Central) - Aug 9, 2020 In summary, PLTs were altered in p53 mice, and the PI3K signaling pathway was involved in that process, suggesting that the p53-dependent PI3K signaling pathway is involved in thrombocytopenia or PLT diseases. PLT number is reduced in p53 deficiency; however, this reduction could be reverted by inhibiting the PI3K pathway.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: 25-OH-PPD inhibits hypertrophy on diabetic cardiomyopathy via the PI3k/Akt/GSK-3β signaling pathway. (Pubmed Central) - Aug 9, 2020 The animals were divided into 5 groups as follows: Normal group (NG group), diabetic group, PPD treatment group, PPD/LY294002 group (inhibitor of PI3K/Akt) and PPD/LiCl group [inhibitor of glycogen synthase kinase (GSK) 3β]...In addition, PPD treatment significantly increased the expression levels of p-Akt and decreased the levels of phosphorylated GSK-3β compared with those of the DMCM group (P<0.05). The data demonstrated that the protective effects of 25-OH-PPD against DMCM may be attributed to the PI3k/Akt/GSK-3β signaling pathway, via the suppression of the α-SMA/VCAM axis and the downregulation of TGF-β1 and CTGF expression.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal, IO Biomarker: Lycopene attenuates high glucose-mediated apoptosis in MPC5 podocytes by promoting autophagy via the PI3K/AKT signaling pathway. (Pubmed Central) - Aug 9, 2020 To explore the effects of Lyc on the PI3K/AKT signaling pathway and autophagy, LY294002 (LY) and 3-methyladenine (3-MA) were used as PI3K and autophagy inhibitors, respectively...In addition, the effects of Lyc on HG-mediated MPC5 podocyte apoptosis were alleviated by 3-MA. Therefore, the present study suggested that Lyc may protect against HG-induced MPC5 podocyte apoptosis by promoting autophagy activity via activation of the PI3K/AKT signaling pathway.
- |||||||||| Review, Journal: Alterations and molecular targeting of the GSK-3 regulator, PI3K, in head and neck cancer. (Pubmed Central) - Aug 8, 2020
In this article, we review the PI3K pathway, mutations of this pathway in HNSCC, drugs that target PI3K, the impact of these agents on the PI3K and GSK-3 signaling axes, ongoing clinical trials evaluating PI3K inhibitors, and the challenges of using these drugs in the clinic. This article is part of a Special Issue entitled: GSK-3 and related kinases in cancer, neurological and other disorders edited by James McCubrey, Agnieszka Gizak and Dariusz Rakus.
- |||||||||| Journal: COL6A3 promotes cellular malignancy of osteosarcoma by activating the PI3K/AKT pathway. (Pubmed Central) - Aug 8, 2020
Moreover, the western blot results suggested that the PI3K/AKT signaling pathway was manipulated by measuring the protein expression of the PI3K/AKT pathway-related markers, due to the COL6A3 inhibition. CONCLUSION COL6A3 plays a crucial role in modulating various aspects of the progression of osteosarcoma, which would provide a potentially effective treatment for osteosarcoma.
- |||||||||| Journal: FAM83A signaling induces epithelial-mesenchymal transition by the PI3K/AKT/Snail pathway in NSCLC. (Pubmed Central) - Aug 7, 2020
Rescue experiment demonstrated that inhibition of either AKT or Snail could partially counteract the promoting effect of FAM83A overexpression in NSCLC metastasis. Taken together, our findings are the first time to demonstrate that increased expression of FAM83A in NSCLC was correlated with EMT and tumor metastasis, which may provide a novel therapeutic target in NSCLC treatment.
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