- |||||||||| Review, Journal: PI3K/Akt/mTOR inhibitors in cancer: At the bench and bedside. (Pubmed Central) - May 7, 2020
Some inhibitors of this pathway are approved by the food and drug administration after their potent activity and their effect overweighed the toxicities/side effects. This review discusses the recent trends in exploiting the PI3K/Akt/mTOR pathway towards the molecular targeted therapy using small molecule inhibitors in human cancer.
- |||||||||| Biomarker, Review, Journal: Recent nanotechnological interventions targeting PI3K/Akt/mTOR pathway: A focus on breast cancer. (Pubmed Central) - May 7, 2020
Development of nanotechnology has provided many interesting avenues to target the PI3K/Akt/mTOR pathway both at the pre-clinical and clinical stages. Therefore, the current review summarizes the underlying mechanism and the importance of targeting PI3K/Akt/mTOR pathway, novel biomarkers and use of nanotechnological interventions in breast cancer.
- |||||||||| Journal: Megalencephaly syndromes associated with mutations of core components of the PI3K-AKT-MTOR pathway: PIK3CA, PIK3R2, AKT3, and MTOR. (Pubmed Central) - May 7, 2020
Our review of published data on these disorders so far shows that mildly activating variants (that are typically constitutional or germline) are associated with diffuse megalencephaly with intellectual disability and/or autism spectrum disorder; moderately activating variants (that are typically high-level mosaic) are associated with megalencephaly with pigmentary abnormalities of the skin; and strongly activating variants (that are usually very low-level mosaic) are associated with focal brain malformations including hemimegalencephaly and focal cortical dysplasia. Accurate molecular diagnosis of these disorders is undoubtedly crucial to more optimally treat children with these disorders using PI3K-AKT-MTOR pathway inhibitors.
- |||||||||| Xtandi (enzalutamide capsule) / Pfizer, Astellas, taselisib (GDC-0032) / Roche
Enrollment change, Trial completion date, Combination therapy, Metastases: Taselisib and Enzalutamide in Treating Patients With Androgen Receptor Positive Triple-Negative Metastatic Breast Cancer (clinicaltrials.gov) - May 7, 2020 P1/2, N=30, Active, not recruiting, No abstract available N=73 --> 30 | Trial completion date: Dec 2021 --> Dec 2020
- |||||||||| Preclinical, Journal: Collagen VI Deficiency Results in Structural Abnormalities in the Mouse Lung. (Pubmed Central) - May 6, 2020
In vitro, COL6 promoted steady-state phospho-paxillin levels and reduced cell density (16% to 28%, P < 0.05) at confluence. Inhibition of PI3K, or its downstream effectors, resulted in increased cell density to a level similar to that seen on matrices lacking COL6.
- |||||||||| quercetin (LY294002) / Eli Lilly
Journal: Piceatannol Suppresses the Proliferation and Induced Apoptosis of Osteosarcoma Cells Through PI3K/AKT/mTOR Pathway. (Pubmed Central) - May 6, 2020 Human osteosarcoma cells in this study were, respectively, treated with PIC at various concentrations (0, 20, 40, 80 μmol/L), PI3K/AKT/mTOR pathway inhibitor (LY294002), or pathway activator (740Y-P) plus PIC...The PI3K/AKT/mTOR pathway was prominently inhibited in PIC-treated osteosarcoma cells and tumor tissues. PIC suppresses the proliferation and induces apoptosis of osteosarcoma cells through regulating PI3K/AKT/mTOR pathway, which is expected to be the therapeutic of osteosarcoma.
- |||||||||| Journal: Potent Antineoplastic Effects of Combined PI3Kα-MNK Inhibition in Medulloblastoma. (Pubmed Central) - May 2, 2020
We also observed a significant reduction in tumor formation in subcutaneous and intracranial mouse xenograft models, which further suggests that this combinatorial approach may represent an efficient therapeutic strategy for medulloblastoma. Implications: These findings raise the possibility of a unique therapeutic approach for medulloblastoma, involving MNK targeting to sensitize medulloblastoma CSCs to PI3Kα inhibition.
- |||||||||| Journal: Downregulation of microRNA-519 enhances development of lung cancer by mediating the E2F2/PI3K/AKT axis. (Pubmed Central) - May 2, 2020
Finally, the extent of PI3K/AKT signaling pathway phosphorylation was examined, which illustrated that upregulation of miR-519 repressed the phosphorylation of the PI3K/AKT pathway in SPC-A-1 and 95C cells. miR-519 reduces PI3K/AKT pathway activities by suppressing the transcription activity of E2F2, thereby potentially inhibiting the occurrence of lung cancer.
- |||||||||| AZD3463 / AstraZeneca
Journal: AZD3463, an IGF-1R inhibitor, suppresses breast cancer metastasis to bone via modulation of the PI3K-Akt pathway. (Pubmed Central) - May 2, 2020 Mechanistic investigations indicated that the apoptosis-inducing activity of AZD3463 could be associated to its role in the activation of the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway. These findings suggested that AZD3463 could serve as a promising therapeutic molecule for treating BM in breast cancer patients, particularly when applied in conjunction with ZA or other antitumor agents.
- |||||||||| PIK-75 / Pathway Therapeutics, Tafinlar (dabrafenib) / Novartis, Zelboraf (vemurafenib) / Roche
Journal: Joint action of miR-126 and MAPK/PI3K inhibitors against metastatic melanoma. (Pubmed Central) - May 1, 2020 Finally, the synergistic role played by miR-126 in combination with vemurafenib and/or PIK-75 was demonstrated in vivo in mouse xenograft models, in which tumor growth inhibition was associated with increased apoptosis. All together, these results not only show the efficacy of PIK-75 and vemurafenib co-treatment, but also indicate that restoration of miR-126 expression in advanced melanoma can enhance their antitumor activity, which may possibly allow dose reduction to decrease adverse events without reducing the therapeutic benefits.
- |||||||||| Journal: CRYAB inhibits migration and invasion of bladder cancer cells through the PI3K/AKT and ERK pathways. (Pubmed Central) - May 1, 2020
All together, these results not only show the efficacy of PIK-75 and vemurafenib co-treatment, but also indicate that restoration of miR-126 expression in advanced melanoma can enhance their antitumor activity, which may possibly allow dose reduction to decrease adverse events without reducing the therapeutic benefits. Overall, the results of our study suggested that alpha-crystallin B may function as a tumour-suppressive factor in bladder cancer.
- |||||||||| Journal: Interferon gamma induces inflammatory responses through the interaction of CEACAM1 and PI3K in airway epithelial cells. (Pubmed Central) - Apr 30, 2020
Overall, the results of our study suggested that alpha-crystallin B may function as a tumour-suppressive factor in bladder cancer. IFN-γ could induce inflammatory responses, cellular growth and proliferation through the interaction of CEACAM1 (especially CEACAM1-S isoforms) and PI3K(p110δ)/Akt/mTOR in airway epithelial cells, which might be new alternative of future therapies against epithelial transition from inflammation to cancer.
- |||||||||| Tevimbra (tislelizumab-jsgr) / BeiGene, Brukinsa (zanubrutinib) / BeiGene, BGB-10188 / BeiGene
Enrollment open, Combination therapy, Monotherapy: BGB-A317-3111-10188-101: Study of BGB-10188 as Monotherapy, and in Combination With Zanubrutinib, and Tislelizumab (clinicaltrials.gov) - Apr 30, 2020 P1/2, N=150, Recruiting, IFN-γ could induce inflammatory responses, cellular growth and proliferation through the interaction of CEACAM1 (especially CEACAM1-S isoforms) and PI3K(p110δ)/Akt/mTOR in airway epithelial cells, which might be new alternative of future therapies against epithelial transition from inflammation to cancer. Not yet recruiting --> Recruiting
- |||||||||| Journal, IO Biomarker: Naringin inhibits colorectal cancer cell growth by repressing the PI3K/AKT/mTOR signaling pathway. (Pubmed Central) - Apr 30, 2020
Naringin promoted the apoptosis of CRC cells and inhibited the activation of the PI3K/AKT/mTOR signaling pathway in a dose-dependent manner. The results demonstrated that naringin may be a promising therapeutic agent for the treatment of CRC, which may inhibit the proliferation of CRC cells and induce apoptosis by inhibiting the PI3K/AKT/mTOR signaling pathway.
- |||||||||| cisplatin / Generic mfg.
Journal: Reversing Acute Kidney Injury Using Pulsed Focused Ultrasound and MSC Therapy: A Role for HSP-Mediated PI3K/AKT Signaling. (Pubmed Central) - Apr 30, 2020 In this study, we studied the effect of bone marrow-derived MSCs (BM-MSCs), in conjunction with pFUS, in a mouse model of cisplatin-induced AKI...Further analysis linked this effect to the upregulation of heat shock protein (HSP)20/HSP40 and subsequent phosphatidylinositol 3-kinase (PI3K)/Akt signaling. In summary, our results suggest that pFUS and BM-MSCs have independent as well as synergistic therapeutic effects in the context of AKI.
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