- |||||||||| quercetin (LY294002) / Eli Lilly, Crixivan (indinavir sulfate) / Merck (MSD)
Journal: Fibroblast growth factor-21 potentiates glucose transport in skeletal muscle fibers. (Pubmed Central) - Aug 7, 2020 The use of PI3K inhibitors such as Wortmannin (100 nM) and LY294002 (50 µM) completely prevented the FGF21-dependent glucose uptake...FGF21 at low concentrations potentiated the effect of insulin on glucose uptake but at high concentrations, completely inhibited the uptake in the presence of insulin. These results suggest that FGF21 regulates glucose uptake by a mechanism mediated by GLUT4 and dependent on atypical PKC-ζ- in skeletal muscle.
- |||||||||| Journal: TRIM21 and PHLDA3 negatively regulate the crosstalk between the PI3K/AKT pathway and PPP metabolism. (Pubmed Central) - Aug 5, 2020
Importantly, PTEN null human cancer cells and in vivo murine models are sensitive to anti-PPP treatments, suggesting the importance of the PPP in maintaining AKT activation even in the presence of a constitutively activated PI3K pathway. Our study suggests that blockade of this reciprocal crosstalk mechanism may have a therapeutic benefit for cancers with PTEN loss or PI3K/AKT activation.
- |||||||||| metformin / Generic mfg.
[VIRTUAL] PI3K–mTOR pathway inhibition. A possible new approach in the fight against glioblastoma (Poster Area) - Aug 5, 2020 - Abstract #ECNP2020ECNP_747; Because invasion is a major obstacle for GB therapy, metformin’s chances as a therapeutic candidate for GB treatment are now in evaluation [5]. Recent evidence pointed out that the blockade of mTORC2 might provide a useful therapeutic strategy for GB, with the potential to overcome the limitations that conventional treatment has shown so far.
- |||||||||| Journal: PTEN Methylation by NSD2 Controls Cellular Sensitivity to DNA Damage. (Pubmed Central) - Aug 4, 2020
More importantly of note, inhibiting NSD2-mediated methylation of PTEN, either through expressing methylation-deficient PTEN mutants, or through inhibiting NSD2, sensitizes cancer cells to combinatorial treatment with PI3K inhibitor and DNA-damaging agents in both cell culture and in vivo xenograft models. Therefore, our study provides a novel molecular mechanism for PTEN regulation of DSBs repair in a methylation- and protein-phosphatase-dependent manner.
- |||||||||| cisplatin / Generic mfg.
Journal: MicroRNA-654-3p enhances cisplatin sensitivity by targeting QPRT and inhibiting the PI3K/AKT signaling pathway in ovarian cancer cells. (Pubmed Central) - Aug 4, 2020 In addition, inhibition of miR-654-3p reversed the suppressive effects of QPRT-targeting short interfering RNA on the proliferation and chemoresistance of ovarian cancer cells. Therefore, the results of the present study revealed a previously unrecognized regulatory mechanism that miR-654-3p enhances DDP sensitivity of OVC cells by downregulating QPRT expression; in addition, the present study highlighted the therapeutic implications of miR-654-3p upregulation in OVC.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: MST4 inhibits human hepatocellular carcinoma cell proliferation and induces cell cycle arrest via suppression of PI3K/AKT pathway. (Pubmed Central) - Aug 4, 2020 Importantly, mechanistic investigations suggested that dnMST4 significantly elevated the phosphorylation levels of key members of PI3K/AKT pathway, and the selective PI3K inhibitor LY294002 can reverse the proliferation-promoting effect of dnMST4. Overall, our results provide a new insight into the clinical significance, functions and molecular mechanism of MST4 in HCC, suggesting that MST4 might have a potential therapeutic value in the HCC clinical treatment.
- |||||||||| Journal: LncZEB1-AS1 regulates hepatocellular carcinoma bone metastasis via regulation of the miR-302b-EGFR-PI3K-AKT axis. (Pubmed Central) - Aug 4, 2020
At a mechanistic level, we found that lncZEB1-AS1 was able to target miR-302b and to thereby increase PI3K-AKT pathway activation and EGFR expression, resulting in the enhanced expression of downstream matrix metalloproteinase genes in HCC cells. In summary, our results provide novel evidence that lncZEB1-AS1 can promote HCC BM through a mechanism dependent upon the activation of PI3K-AKT signaling, thus highlighting a potentially novel therapeutic avenue for the treatment of such metastatic progression in HCC patients.
- |||||||||| Journal, PD(L)-1 Biomarker, IO Biomarker: Clinicopathological and Preclinical Findings of NUT Carcinoma: A Multicenter Study. (Pubmed Central) - Aug 2, 2020
Among MYC-targeting agents, including BET and HDAC inhibitors, CUDC-907 (a dual PI3K/HDAC inhibitor) was most effective against NC cells, followed by panobinostat (an HDAC inhibitor) and AZD5153 (a bivalent BET inhibitor). CUDC-907 might be promising in NC treatment.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal: The Role of PI3K Inhibition in Lymphoid Malignancies. (Pubmed Central) - Aug 2, 2020 Preclinical models are helpful in predicting possible side effects and identifying new lymphoma subtypes that may be susceptible to this class of agents. The future will likely involve rationally designed combinatorial approaches to deepen the response rate and prevent the emergence of resistance.
- |||||||||| Journal: Dysregulated actin dynamics in activated PI3Kδ syndrome. (Pubmed Central) - Aug 2, 2020
We report a patient with APDS who had widespread necrotic skin lesions that were responsive specifically to immunosuppressive therapy. EBV-transformed lymphoblastoid cells (EBV-LCLs) from patients with APDS exhibit increased polymerized actin and increased apoptosis, suggesting a contribution of impaired actin dynamics to this disease.
- |||||||||| Journal: A novel PI3K/mTOR dual inhibitor XH002 exhibited robust antitumor activity in NSCLC. (Pubmed Central) - Jul 31, 2020
Moreover, XH002 remarkably inhibited tumor growth of EGFR-TKIs resistant NCI-H1975 xenograft model by blocking PAM pathway. In conclusion, XH002 is a potent oral PI3K/mTOR dual inhibitor that possess excellent antitumor efficacy against PIK3CA mutant NSCLC, including which resistant to EGFR-TKIs treatments.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: PEAR1 suppresses the proliferation of pulmonary microvascular endothelial cells via PI3K/AKT pathway in ALI model. (Pubmed Central) - Jul 31, 2020 Thus, we speculated that rutin could increase the activation of PI3K/AKT/mTOR signaling pathway, further decrease the oxidative stress level via increasing the expression of anti-oxidative stress enzymes with the increasing in concentration of angiogenesis promoting factors, resulting in the protective role in cardiomyocytes and cardiac function. PEAR1 acts as a negative regulator in the proliferation of HPMECs in ALI model via the PI3K/AKT pathway.
- |||||||||| Journal: Molecular profiling of CNS tumors for the treatment and management of disease. (Pubmed Central) - Jul 31, 2020
CDK4/6 and PI3K inhibitors were among the most commonly reported drug class with FDA approved therapies and investigational therapies, which is consistent with the frequencies of these genes in our cohort. Overall, our study established the molecular profiles of glioblastoma based on the 2017 joint consensus guidelines by AMP/ASCO/CAP and provides the potential implications for targeted therapeutic options currently available.
|