- |||||||||| Review, Journal: Infectious Complications of Targeted Therapies for Solid Cancers or Leukemias/Lymphomas. (Pubmed Central) - Apr 13, 2023
Infections, particularly fungal ones, are common in patients treated with BTK inhibitors even though most of the complications occurring among patients treated by ICIs or CART-cells infusion are associated with the treatment of side effects related to the use of these new treatments. The diagnosis of these infectious complications can be difficult and may require extensive investigations.
- |||||||||| Ibrance (palbociclib) / Pfizer, buparlisib (AN2025) / Novartis, Adlai Nortye
Preclinical, Journal: Prognostic Relevance and In Vitro Targeting of Concomitant PTEN and p16 Deficiency in Chordomas. (Pubmed Central) - Apr 13, 2023 Synergistic effects were observed when combining palbociclib with rapamycin. In conclusion, we show that patients with PTEN-/p16-negative chordomas have poor prognoses and provide strong preclinical evidence that these patients might benefit from a Palbociclib/rapamycin combination treatment.
- |||||||||| Surfactant lipids inhibit PI3K-dependent signaling pathways induced by IL-4 in alveolar macrophages (P711) (Exhibit Hall; Poster Board No. P711) - Apr 11, 2023 - Abstract #IMMUNOLOGY2023IMMUNOLOGY_2008;
Lipid-dependent inhibition of the Akt/mTORC1 signaling axis is consistent with reduced IL-4+SP-A-driven glycolysis and mitochondrial respiration as well as decreased ATP citrate lyase expression and histone acetylation stimulated by IL-4. We conclude that surfactant lipids inhibit PI3K-dependent signaling pathways and suggest that decrease of surfactant lipids in chronic lung diseases might augment IL-4-dependent fibrotic responses.
- |||||||||| Treatment of non-Hodgkin lymphoma with targeted drugs may include: * PI3K inhibitors, such as duvelisib, tenalisib, and buparlisib, * BTK (Bruton tyrosine kinase) inhibitors, such as ibrutinib, * BSL-2 inhibitors, such as venetoclax, * Janus kinase inhibitors such as ruxolitinib, (Twitter) - Apr 8, 2023
- |||||||||| LY294002 / Eli Lilly
Journal: Combination of PDGF-BB and adipose-derived stem cells accelerated wound healing through modulating PTEN/AKT pathway. (Pubmed Central) - Apr 8, 2023 The role of PRP, PDGF-BB, and PDGF-BB combined with a PI3k inhibitor LY294002 on the viability, migration, and PTEN/AKT pathway in ADSCs were examined utilizing CCK-8, Transwell, and western blot assays...Moreover, combined intervention with ADSCs and PDGF-BB attenuated the PTEN level and elevated the CD31 level as well as the ratio of p-AKT/AKT in the skin tissues. A combination of ADSCs and PDGF-BB facilitated wound healing might associate with the regulation of the PTEN/AKT pathway.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal, IO biomarker: Kaempferol ameliorates pulmonary vascular remodeling in chronic hypoxia-induced pulmonary hypertension rats via regulating Akt-GSK3?-cyclin axis. (Pubmed Central) - Apr 7, 2023 Furthermore, primary rat PASMCs were exposed to hypoxic conditions to generate a cell proliferation model, then incubated with either kaempferol or LY294002 (an inhibitor of PI3K)...The mechanistic analysis demonstrated that kaempferol reduced the protein levels of phosphorylation of Akt and GSK3?, leading to decreased expression of pro-proliferation (CDK2, CDK4, Cyclin D1, and PCNA) and anti-apoptotic related proteins (Bcl-2) and increased expression of pro-apoptosis proteins (Bax and cleaved caspase 3). These results collectively demonstrate that kaempferol ameliorates HPH in rats by inhibiting PASMC proliferation and pro-apoptosis via modulation of the Akt/GSK3?/CyclinD axis.
- |||||||||| Journal: p85? regulatory subunit isoform controls PI3-kinase and TRPC6 membrane translocation. (Pubmed Central) - Apr 4, 2023
in controlling translocation of PI3K from the cytosol to the plasma membrane and PI3K-mediated TRPC externalization by oxidized lipids. Current PI3K inhibitors block the catalytic subunit, but our data suggest that the regulatory subunit is a novel therapeutic target to promote EC migration and healing after arterial injuries that occur with angioplasty.
- |||||||||| AZD4573 / AstraZeneca
Journal: CDK9 inhibition induces epigenetic reprogramming revealing strategies to circumvent resistance in lymphoma. (Pubmed Central) - Apr 4, 2023 Here we show that AZD4573, a selective inhibitor of CDK9, restricted growth of DLBCL cells...Thus, CDK9i induces reprogramming of the epigenetic landscape, and super-enhancer driven recovery of select oncogenes may contribute to resistance to CDK9i. PIM and PI3K represent potential targets to circumvent resistance to CDK9i in the heterogeneous landscape of DLBCL.
- |||||||||| buparlisib (AN2025) / Novartis, Adlai Nortye
Journal: ABL1 kinase as a tumor suppressor in AML1-ETO and NUP98-PMX1 leukemias. (Pubmed Central) - Mar 29, 2023 PI3K inhibitor buparlisib exerted selective activity against Lin-cKit+ NUP98-PMX1;Abl1-/- cells when compared to the Abl1?+?/+ counterparts...Moreover, ABL1 kinase inhibitor enhanced the sensitivity to PI3K, DNA-PKcs and ATR inhibitors. In conclusion, we showed that ABL1 kinase plays a tumor suppressor role in hematological malignancies induced by AML1-ETO and NUP98-PMX1 and modulates the response to PI3K and/or DDR inhibitors.
- |||||||||| Piqray (alpelisib) / Novartis
Journal: Targeting MLL Methyltransferases Enhances the Antitumor Effects of PI3K Inhibition in Hormone Receptor-positive Breast Cancer. (Pubmed Central) - Mar 28, 2023 The high frequency of aberrant PI3K pathway activation in hormone receptor-positive (HR) breast cancer has led to the development, clinical testing, and approval of the p110?-selective PI3K inhibitor alpelisib...Dual PI3K and MLL inhibition synergize to reduce clonogenicity and cell proliferation, and promote in vivo tumor regression. These findings suggest patients with PIK3CA-mutant, HR breast cancer may derive clinical benefit from combined PI3K/MLL inhibition.
- |||||||||| Review, Journal: Diagnosis and Treatment of Chronic Lymphocytic Leukemia: A Review. (Pubmed Central) - Mar 25, 2023
In patients with multiple relapses, chimeric antigen receptor T-cell (CAR-T) therapy with lisocabtagene maraleucel was associated with a 45% complete response rate...Approximately two-thirds of patients eventually need treatment. Highly effective novel targeted agents include BTK inhibitors such as acalabrutinib, zanubrutinib, ibrutinib, and pirtobrutinib or BCL2 inhibitors such as venetoclax.
- |||||||||| LY294002 / Eli Lilly
SULFATE-REDUCING BACTERIA INDUCE TNF-? EXPRESSION IN A PI3 KINASE/AKT PATHWAY-DEPENDENT MANNER (South Hall A, Poster Hall - McCormick Place) - Mar 23, 2023 - Abstract #DDW2023DDW_6485; expression, we treated the cells with a PI3K inhibitor LY294002 and assessed the level of protein expression and phosphorylation status...Thus, our study identified a novel pathway that may be targeted to inhibit inflammation seen in conditions with SRB overgrowth. This study was supported by the Winkler Bacterial Overgrowth Research Fund.
- |||||||||| Journal: Design and Discovery of Novel Cyclic Peptides as EDPs-EBP Interaction Inhibitors for the Treatment of Liver Fibrosis. (Pubmed Central) - Mar 21, 2023
The subsequent in vivo study demonstrated that C-2 possessed potent antifibrotic efficacy in ameliorating CCl-induced liver fibrosis. This work provides a successful pharmacological strategy for the development of novel inhibitors of EDPs-EBP interaction, which sheds new light on how cyclic peptides disrupt peptide-protein interaction and may also provide new structure-oriented therapeutic candidates in liver fibrosis.
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