- |||||||||| Synribo (omacetaxine mepesuccinate) / Stragen, Teva
Journal, IO Biomarker: Homoharringtonine suppresses LoVo cell growth by inhibiting EphB4 and the PI3K/AKT and MAPK/EKR1/2 signaling pathways. (Pubmed Central) - Apr 14, 2020 HHT inhibited EphB4 downstream pathways such as PI3K/AKT and MAPK/EKR1/2, resulting in the regulation of cell cycle-related molecules (cyclinA2 and CDC2), and the molecules in the Bcl-2 mitochondrial apoptosis pathway including Bcl-2, Mcl-1, Bax, Bad, caspase-3, caspase-7, and caspase-9. HHT may therefore be a promising EphB4 inhibitor with great potential for CRC treatment.
- |||||||||| Journal: Ras-PI3K pathway promotes osteosarcoma progression via regulating VRK1-mediated H2A phosphorylation at threonine 120. (Pubmed Central) - Apr 14, 2020
Ras-PI3K pathway activation promoted osteosarcoma progression might be via up-regulating VRK1-mediated H2A. We proposed that VRK1 and H2A could be the potential targets for osteosarcoma diagnosis and treatment.HighlightsH2A is specifically promoted by Ras-PI3K pathway activation.H2A joins in the oncogenic effects of Ras-PI3K pathway on osteosarcoma.H2A regulates the transcription of Ras-PI3K-targeted genes.VRK1 takes part in the regulatory function of Ras-PI3K pathway on H2A.
- |||||||||| Opdivo (nivolumab) / Ono Pharma, BMS, Copiktra (duvelisib) / Verastem
[VIRTUAL] Synergistic anti-tumor efficacy of the dual PI3K-δ/PI3K-γ inhibitor duvelisib with PD-1 blockade in solid tumor and lymphoma models (Virtual Meeting: All Session Times Are U.S. EDT) - Apr 13, 2020 - Abstract #AACRI2020AACR-I_447; P1 Taken together, these data indicate the value of dual PI3K-δ,γ inhibition for combination with PD-1 blockade and support clinical evaluation of duvelisib with anti-PD-1 in patients with solid tumors or hematologic malignancies. Clinical studies are underway investigating the combination of duvelisib plus nivolumab in aggressive lymphomas (Richter’s transformation or transformed FL; NCT03892044) and duvelisib plus pembrolizumab in head and neck squamous cell carcinoma.
- |||||||||| [VIRTUAL] Regulation of PTEN translation by PI3K signaling maintains pathway homeostasis (Virtual Meeting: All Session Times Are U.S. EDT) - Apr 13, 2020 - Abstract #AACRI2020AACR-I_174;
Regulation of expression is due to mTOR/4EBP1 dependent control of PTEN translation and is lost when 4EBP1 is knocked out. Translational regulation of PTEN is therefore a major homeostatic regulator of physiologic PI3K signaling and plays a role in reducing the output of oncogenic mutants that deregulate the pathway and the antitumor activity of PI3K pathway inhibitors.
- |||||||||| Journal: Cross-talk between Rho GTPases and PI3K in the Neutrophil. (Pubmed Central) - Apr 12, 2020
Here we review cross-talk between these important signaling intermediates in the context of neutrophil functions. We include PI3K-dependent activation of Rho family small GTPases and of their guanine nucleotide exchange factors and GTPase activating proteins, as well as Rho GTPase-dependent regulation of PI3K.
- |||||||||| Pletal (cilostazol) / Otsuka
Journal: Role of Nrf2/HO-1 and PI3K/AKT Genes In The Hepatoprotective Effect of cilostazol. (Pubmed Central) - Apr 12, 2020 Cilostazol administration ameliorated TAA-induced liver injury, where it caused a significant improvement in the activity liver enzymes as well as in the histopathological changes. Such effect was associated with a significant increase in the expression of PI3K/Akt and Nrf2/HO-1 mRNAs as detected by Real-time reverse transcription polymerase chain reaction (RT-PCR).
- |||||||||| Journal, PARP Biomarker, IO Biomarker: GAB2 inhibits chondrocyte apoptosis through PI3K-AKT signaling in osteoarthritis. (Pubmed Central) - Apr 11, 2020
Moreover, GAB2 knockdown inhibited AKT phosphorylation, increased BAX expression, and decreased BCL2 expression, which indicated that GAB2 regulates chondrocyte apoptosis through PI3K-AKT signaling. Taken together, our study indicates that GAB2 plays a vital role in chondrocyte apoptosis and provides a new therapeutic target for OA.
- |||||||||| Preclinical, Journal: Anticancer activity of THMPP: Downregulation of PI3K/ S6K1 in breast cancer cell line. (Pubmed Central) - Apr 11, 2020
QSAR and ADME analysis proved THMPP as an effective anti-breast cancer drug, exhibiting important pharmacological properties. Overall, the results suggest that THMPP induced cell death might be regulated by EGFR signaling pathway which augments THMPP being developed as a potential candidate for treating breast cancer.
- |||||||||| SF2523 / SignalRx Pharma
Journal: SF2523: Dual PI3K/BRD4 inhibitor blocks tumor immunosuppression and promotes adaptive immune responses in cancer. (Pubmed Central) - Apr 10, 2020 Pharmacological inhibition of BRD4 using JQ1 and/or PI3K using dual PI3K/BRD4 inhibitor SF2523 (previously reported by our group as a potent inhibitor to block tumor growth and metastasis in various cancer models) suppresses tumor growth in syngeneic and spontaneous murine cancer models; reduces infiltration of myeloid-derived suppressor cells (MDSCs); blocks polarization of immunosuppressive macrophages; restores CD8+ T-cell activity and stimulates anti-tumor immune responses. Finally, our results suggest that BRD4 regulates the immunosuppressive myeloid tumor microenvironment and BET inhibitors and dual PI3K/BRD4 inhibitors are therapeutic strategies for cancers driven by the macrophage-dependent immunosuppressive TME.
- |||||||||| pictilisib (GDC-0941) / Roche, capivasertib (AZD5363) / Otsuka, AstraZeneca
Journal: Design and characterization of SGK3-PROTAC1, an isoform specific SGK3 kinase PROTAC degrader. (Pubmed Central) - Apr 10, 2020 This work underscores the benefit of the PROTAC approach in targeting protein kinase signaling pathways with greater efficacy and selectivity than can be achieved with conventional inhibitors. SGK3-PROTAC1 will be an important reagent to explore the roles of the SGK3 pathway.
- |||||||||| Journal: Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors. (Pubmed Central) - Apr 10, 2020
The biochemical mechanisms of dual mutations include increased disruption of p110α binding to the inhibitory subunit p85α, which relieves its catalytic inhibition, and increased p110α membrane lipid binding. Double PIK3CA mutations predict increased sensitivity to PI3Kα inhibitors compared with single-hotspot mutations.
- |||||||||| Review, Journal: Mutation-Driven Signals of ARID1A and PI3K Pathways in Ovarian Carcinomas: Alteration Is An Opportunity. (Pubmed Central) - Apr 10, 2020
In this review, we present the data demonstrating the co-occurrence of mutations of ARID1A and the PI3K pathway in our cohort of ovarian cancers from the Avera Cancer Institute (SD, USA). Taking into account data from our cohort and the cBioPortal, we interrogate the opportunity provided by this co-occurrence in the context of mutation-driven signals in the life cycle of a tumor cell and its response to the targeted anti-tumor drugs.
- |||||||||| Review, Journal: PI3K/mTOR Pathway Inhibition: Opportunities in Oncology and Rare Genetic Diseases. (Pubmed Central) - Apr 10, 2020
This group of syndromes presents with additional neurological manifestations associated with epilepsy and other neuropsychiatric symptoms induced by neuronal mTOR pathway hyperactivation. While PI3K and mTOR inhibitors have been and still are intensively tested in oncology indications, their use in genetically defined syndromes and mTORopathies appear to be promising avenues for a pharmacological intervention.
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