- |||||||||| Review, Journal: Immuno-Metabolism and Microenvironment in Cancer: Key Players for Immunotherapy. (Pubmed Central) - Feb 10, 2021
The most successful strategy to date has been the combination of antiangiogenic drugs and ICIs, which prolonged the survival of patients with non-small-cell lung cancer (NSCLC) and hepatocellular carcinoma (HCC), while results from tryptophan pathway inhibition studies are inconclusive. New exciting strategies include targeting the adenosine pathway, TAMs and the microbiota with fecal microbiome transplantation.
- |||||||||| buparlisib (BKM120) / Novartis, Adlai Nortye
Journal: PI3K abrogation using pan PI3K inhibitor BKM120 give rise to a weighty anti-cancer effect on AML-derived KG-1 cells by inducing apoptosis and G2/M arrest (Pubmed Central) - Feb 9, 2021 Interestingly, we found that the single agent of BKM120 was unable to significantly alter the expression level of c-Myc; however, the capability of BKM120 to reduce the survival rate of AML cells was potentiated upon c-Myc inhibition using 10058-F4; suggestive of the plausible contribution of c-Myc in leukemic cell response to the PI3K inhibitor. Taken together, the results of this study declared the efficacy of BKM120 as a therapeutic approach for AML; however, further investigations should be accomplished to determine the expediency of this inhibitor.
- |||||||||| Preclinical, Journal, PARP Biomarker: Calycosin induces apoptosis in osteosarcoma cell line via ERβ‑mediated PI3K/Akt signaling pathways. (Pubmed Central) - Feb 9, 2021
ERβ‑mediated PI3K/Akt downstream signaling pathways were found to influence the activity of poly (ADP‑ribose) polymerase 1 and caspase‑3. Thus, the present results indicated that calycosin inhibited proliferation and induced apoptosis in OS MG‑63 cells, and that these effects were mediated by ERβ‑dependent inhibition of the PI3K/Akt pathways.
- |||||||||| pictilisib (GDC-0941) / Roche
Clinical, Journal, Combination therapy: GDC-0941 and CXCL8 (3-72) K11R/G31P combination therapy confers enhanced efficacy against breast cancer. (Pubmed Central) - Feb 9, 2021 Furthermore, the migration ability of the breast cancer cell lines were significantly curtailed by the combination therapy compared with the single treatments. The findings suggest that combination treatment involving PI3K inhibitor and CXCR1/2 analogue (G31P) could be a potent therapeutic option for breast cancer treatment.
- |||||||||| Review, Journal: Phosphatidylinositol-3-Kinase Inhibition in Follicular Lymphoma. (Pubmed Central) - Feb 9, 2021
Response rates in highly refractory disease are high, demonstrate few long-term remissions, and have high long-term toxicity. Early data on dosing and combination strategies are promising and may change how we use these agents in the coming years.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Review, Journal: Novel Agents Beyond Immunomodulatory Agents and Phosphoinositide-3-Kinase for Follicular Lymphoma. (Pubmed Central) - Feb 9, 2021 Although median overall survival rates exceed 12 years with rituximab, follicular lymphoma remains largely incurable...Prognostic markers have identified a subset of patients with chemoresistant and/or refractory disease-associated poor outcomes. We identify the patients with follicular lymphoma in need of novel therapies, describe the drivers of lymphomagenesis and importance of the tumor microenvironment, and summarize the novel agents under investigation in relapsed/refractory and upfront follicular lymphoma.
- |||||||||| Journal: The complex balance of PI3K inhibition. (Pubmed Central) - Feb 9, 2021
The mechanism of polydatin to alleviate atherosclerotic lesions was achieved by autophagic restoration. No abstract available
- |||||||||| Journal: Alt-RPL36 downregulates the PI3K-AKT-mTOR signaling pathway by interacting with TMEM24. (Pubmed Central) - Feb 9, 2021
These results implicate alt-RPL36 as an upstream regulator of PI3K-AKT-mTOR signaling. More broadly, the RPL36 transcript encodes two sequence-independent polypeptides that co-regulate translation via different molecular mechanisms, expanding our knowledge of multicistronic human gene functions.
- |||||||||| Review, Journal: DOK7 Inhibits Cell Proliferation, Migration, and Invasion of Breast Cancer via the PI3K/PTEN/AKT Pathway. (Pubmed Central) - Feb 9, 2021
Repression of PTEN expression using PTEN siRNA or SF1670 (PTEN inhibitor) rescued the tumor-inhibiting effect induced by DOK7 overexpression, suggesting that DOK7 inhibits proliferation, migration, and invasion of breast cancer cells though the PI3K/PTEN/AKT pathway. These results suggest that the downregulation of DOK7 may become a novel breast cancer therapeutic target.
- |||||||||| ZSTK474 / Zenyaku Kogyo
Journal: The Antileukemia Activity of ZSTK474 on U937 Cells (Pubmed Central) - Feb 9, 2021 Our data indicated that circCOL5A1 might serve as a novel promising therapeutic target and represent a new avenue to understand underlying pathogenesis for keloids. ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells.
- |||||||||| Journal, PARP Biomarker, IO biomarker: Costunolide Induces Apoptosis of K562/ADR Cells through PI3K/AKT Pathway (Pubmed Central) - Feb 9, 2021
ZSTK474 can inhibit the pathway of PI3K/AKT, ZSTK474 alone or in combination with Homoharringtonine shows potential antileukemia activity on U937 cells. Costunolide could inhibit the proliferation and apoptosis of K562/ADR cells through regulation of PI3K/AKT pathway.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
[VIRTUAL] The Functional GRHL3-FLG Axis Predicts Targeted Therapy Response in Head and Neck Cancer () - Feb 8, 2021 - Abstract #TAT2021TAT_142; To date, in addition to the non-selective conventional HNSCC treatments, such as chemotherapies and surgeries, the only FDA-approved targeted therapy Cetuximab, an epidermal growth factor receptor inhibitor, has a low response rate with considerable toxicity...Moreover, the loss of FLG in sensitive HNSCC cells resulted in a dramatic resistance to targeted therapies while the GRHL3hi-FLGwt signature predicted a favourable patient's prognosis. Conclusions Functional differentiation (GRHL3hi-FLGwt) provides the first example of differentiation-dependent therapy response and establishes a rationale for clinical investigation of differentiation-paired targeted therapy that may improve outcomes in HNSCC and other heterogeneous cancers.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
[VIRTUAL] The Functional GRHL3-FLG Axis Predicts Targeted Therapy Response in Head and Neck Cancer () - Feb 8, 2021 - Abstract #TAT2021TAT_38; To date, in addition to the non-selective conventional HNSCC treatments, such as chemotherapies and surgeries, the only FDA-approved targeted therapy Cetuximab, an epidermal growth factor receptor inhibitor, has a low response rate with considerable toxicity...Moreover, the loss of FLG in sensitive HNSCC cells resulted in a dramatic resistance to targeted therapies while the GRHL3hi-FLGwt signature predicted a favourable patient's prognosis. Conclusions Functional differentiation (GRHL3hi-FLGwt) provides the first example of differentiation-dependent therapy response and establishes a rationale for clinical investigation of differentiation-paired targeted therapy that may improve outcomes in HNSCC and other heterogeneous cancers.
- |||||||||| quercetin (LY294002) / Eli Lilly
Preclinical, Journal: 1,25(OH)D Strengthens the Vasculogenesis of Multipotent Mesenchymal Stromal Cells from Rat Bone Marrow by Regulating the PI3K/AKT Pathway. (Pubmed Central) - Feb 5, 2021 Western blotting and gelatin zymography were used to detect the expression and activities of VEGF, MMP-2 and MMP-9 secreted by MSCs under the influence of 1,25(OH)D Finally, the VDR antagonist pyridoxal-5-phosphate (P5P) and the PI3K/AKT pathway inhibitor LY294002 were utilized to test the phosphorylation levels of key kinases in the PI3K/AKT pathway by Western blotting and the formation of capillary-like structures in Matrigel...In addition, the ability to form capillary-like structures was reduced when the VDR and PI3K/AKT pathways were blocked. This study confirmed that 1,25(OH)D treatment can strengthen the ability of MSCs to promote vasculogenesis in vitro, and the mechanism may be related to the activation of the PI3K/AKT pathway.
- |||||||||| methamphetamine / Generic mfg.
Journal: TBHQ Attenuates Neurotoxicity Induced by Methamphetamine in the VTA through the Nrf2/HO-1 and PI3K/AKT Signaling Pathways. (Pubmed Central) - Feb 5, 2021 These changes were reversed by treatment with the antioxidant TBHQ. The results indicate that TBHQ can enhance Nrf2-induced antioxidative stress and PI3K-induced antiapoptotic effects, which can alleviate METH-induced ROS and apoptosis, and that the crosstalk between Nrf2 and PI3K/AKT is likely the key factor involved in the protective effect of TBHQ against METH-induced chronic nervous system toxicity.
- |||||||||| Journal: The RNA-binding protein Cpeb4 is a novel positive regulator of osteoclast differentiation. (Pubmed Central) - Feb 5, 2021
Loss-of-function analysis showed that shRNA-mediated Cpeb4 depletion strongly impaired TRAP-positive osteoclast formation and expression of key differentiation markers including Acp5, Ctsk, Nfatc1 and Dcstamp. These results suggest that Cpeb4 is a positive regulator in osteoclastogenesis downstream of RANKL signaling.
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