- |||||||||| AKT pathway (Stars at Night Ballroom 3-4) - Sep 12, 2023 - Abstract #SABCS2023SABCS_108;
- |||||||||| PI3 Kinase (Stars at Night Ballroom 3-4) - Sep 12, 2023 - Abstract #SABCS2023SABCS_107;
- |||||||||| Vanflyta (quizartinib) / Daiichi Sankyo
Journal, Combination therapy: Improved efficacy of quizartinib in combination therapy with PI3K inhibition in primary FLT3-ITD AML cells. (Pubmed Central) - Sep 11, 2023
We show here that BAY-806946 enhanced quizartinib cytotoxicity and, most importantly, that this combination increases the ability of quizartinib to kill CD34 CD38leukemia stem cells, whilst sparing normal hematopoietic stem cells. Because constitutively active FLT3 receptor tyrosine kinase is known to boost aberrant PI3K signaling, the increased sensitivity of primary cells to the above combination can be the mechanistic results of the disruption of signaling by vertical inhibition.
- |||||||||| Genetic Profiling and Drug Response Analysis in Multiple Myeloma: Insights for Personalized treatment approaches. (Trianti Upper Foyer; In Person) - Sep 10, 2023 - Abstract #IMW2023IMW_652;
Addressing potential vulnerabilities created by common mechanisms of resistance may be more widely applicable than targeting rare activating mutations in RRMM. Therefore, by leveraging targeted therapy, patients can achieve favourable treatment responses, thus enabling them to gain access to subsequent immunotherapy options and maximize their therapeutic benefits.
- |||||||||| Journal: Germacrone mitigates cardiac remodeling by regulating PI3K/AKT-mediated oxidative stress, inflammation, and apoptosis. (Pubmed Central) - Sep 9, 2023
Mechanistically, germacrone reduced cardiac remodeling-induced activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and the cardioprotective effects of germacrone were abrogated by a PI3K agonist. In conclusion, our results suggest that germacrone attenuates oxidative stress, inflammation, and apoptosis in cardiac remodeling by inhibiting the PI3K/AKT pathway, and may therefore represent a promising therapeutic approach for the treatment of cardiac remodeling.
- |||||||||| Journal: PIK3CA mutations in cutaneous squamous cell carcinoma. (Pubmed Central) - Sep 7, 2023
Although additional basic researches and clinical trials are necessary, various inhibitors may be effective therapeutics for PIK3CA mutation-positive cSCC. Our study revealed the prevalence of PIK3CA mutations in cSCC.
- |||||||||| Review, Journal: PI3K signaling-regulated metabolic reprogramming: From mechanism to application. (Pubmed Central) - Sep 7, 2023
Thus, PI3K inhibitor could effectively regulate metabolic pathway and impede the oncogenic process and some key metabolic proteins or critical enzymes also constitute biomarkers for tumor diagnosis and treatment. In the current review, we summarize the significant effect of PI3K/AKT signaling toward tumor metabolism, it enables us to obtain the better understanding for this interaction and develop more effective therapeutic strategies targeting cancer cell metabolism.
- |||||||||| LY294002 / Eli Lilly, PD98059 / Wayne State University
Journal: Astragaloside IV attenuates high glucose-induced NF-?B-mediated inflammation through activation of PI3K/AKT-ERK-dependent Nrf2/ARE signaling pathway in glomerular mesangial cells. (Pubmed Central) - Sep 7, 2023
Furthermore, phosphatidylinositide 3-kinases (PI3K)/serine/threonine protein kinase (Akt) and extracellular regulated protein kinases (ERK) signaling pathway regulated the process of AS-IV-induced Nrf2 activation and antioxidant capacity, which evidenced by using PI3K inhibitor LY294002 or ERK inhibitor PD98059 that largely abolished the AS-IV efficacy. Taken together, these results indicated that AS-IV protected against HG-induced GMCs damage by inhibiting ROS/NF-kB-induced increases of inflammatory cytokines, fibrosis biomarkers, and cell proliferation via up-regulation of Nrf2-dependent antioxidant enzyme expression, which were mediated by PI3K/Akt and ERK signaling pathway activation.
- |||||||||| Journal: CD73 mitigates hepatic damage in alcoholic steatohepatitis by regulating PI3K/AKT-mediated hepatocyte pyroptosis. (Pubmed Central) - Sep 7, 2023
Taken together, these results indicated that AS-IV protected against HG-induced GMCs damage by inhibiting ROS/NF-kB-induced increases of inflammatory cytokines, fibrosis biomarkers, and cell proliferation via up-regulation of Nrf2-dependent antioxidant enzyme expression, which were mediated by PI3K/Akt and ERK signaling pathway activation. Our results show a novel function of CD73 regulates hepatocytes pyroptosis and highlights the therapeutic opportunity for reducing the disease process in ALD.
- |||||||||| LY294002 / Eli Lilly
Journal: Expressions of sugar transporter genes during Bombyx mori embryonic development. (Pubmed Central) - Sep 7, 2023
The addition of LY294002 (a specific phosphatidylinositol 3-kinase [PI3K] inhibitor) and U0126 (a mitogen-activated protein kinase/extracellular signal-regulated kinase [ERK] kinase [MEK] inhibitor) partially inhibited Tret1 gene expression in dechorionated eggs, but did not affect either ecdysteroid-phosphate phosphatase gene expression or ecdysteroid biosynthesis, clearly indicating that both PI3K and ERK are involved in increased gene expression of Tret1 that was independent of ecdysteroid levels. To our knowledge, this is the first comprehensive report to demonstrate the transcriptional regulation of St genes during embryonic development, thus providing useful information for a clearer understanding of insect egg diapause mechanisms.
- |||||||||| Review, Journal: Current Treatment Options in Relapsed and Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: a Review. (Pubmed Central) - Sep 7, 2023
In absence of a clinical trial, these patients can be challenged with PI3K inhibitors, though responses are usually not durable, and toxicity is high. Combination cytotoxic chemotherapy with novel agents, allogeneic hematopoietic stem cell transplant, and cellular therapy may be considered for very high-risk populations, such as patients with Richter's transformation, though novel approaches are urgently needed and clinical trial enrollment is highly encouraged.
- |||||||||| Imbruvica (ibrutinib) / AbbVie, J&J
Preclinical, Journal: Ibrutinib impairs IGF-1-dependent activation of intracellular Ca handling in isolated mouse ventricular myocytes. (Pubmed Central) - Sep 1, 2023
Acalabrutinib induced similar effects on Ca handling in IGF-1 treated cultured myocytes as Ibrutinib in regard to decreased Ca transient amplitude and slowed Ca transient decay, hence implying a functional class effect of BTK inhibitors in cardiac myocytes. Inhibition of BTK by Ibrutinib impairs IGF-1-dependent activation of intracellular Ca handling in adult ventricular mouse myocytes in the face of disrupted Akt signaling and absent SERCA2a upregulation.
- |||||||||| LY294002 / Eli Lilly
Preclinical, Journal: FGF21 promotes myocardial angiogenesis and mediates the cardioprotective effects of exercise in myocardial infarction mice. (Pubmed Central) - Sep 1, 2023
In vitro, human umbilical vein endothelial cells (HUVECs) were treated with HO, recombinant human FGF21 (rhFGF21), fibroblast growth factor receptor 1 (FGFR1) inhibitor (PD166866), and phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002) to explore the potential mechanisms...Under the intervention of HO, rhFGF21 also played the role of promoting angiogenesis and cell migration through the same mechanism. In conclusion, our results showed that FGF21 promoted the aerobic exercise-induced angiogenesis and improved cardiac function via FGFR1/PI3K/ AKT/VEGF signal in MI mice.
- |||||||||| Journal: MiR-297 inhibits tumour progression of liver cancer by targeting PTBP3. (Pubmed Central) - Aug 31, 2023
Furthermore, in vitro cell experiments confirmed that overexpression of miR-297 could inhibit the PI3K/AKT signaling pathway by down-regulating PTBP3 expression, thereby inhibiting the proliferation, migration and invasion of HCC cells. In conclusion, our results revealed that miR-297 could down-regulate the expression of PTBP3 and inhibit the activation of PI3K/AKT signaling pathway, thereby preventing HCC growth, migration and invasion.
- |||||||||| Journal: Gi/o GPCRs drive the formation of actin-rich tunneling nanotubes in cancer cells via a G??/PKC?/FARP1/Cdc42 axis. (Pubmed Central) - Aug 31, 2023
Consistent with the established role of Rho small GTPases in the formation of actin-rich projecting structures, we identified the PI3K-regulated guanine nucleotide exchange factor (GEF) FARP1 as a GPCR effector essential for TNT formation, acting via Cdc42. Altogether, our study pioneers a link between Gi/o-coupled GPCRs and TNT development, and sheds light into the intricate signaling pathways governing the generation of specialized actin-rich elongated structures in response to bioactive signaling lipids.
- |||||||||| Rituxan (rituximab) / Biogen, Zenyaku Holdings, Roche
Review, Journal, IO biomarker: Treatment of older patients with mantle cell lymphoma in the era of novel agents. (Pubmed Central) - Aug 31, 2023
In the last several years, there is a major trend toward chemotherapy-free regimens, targeted therapies such as BTK, BCL-2 and PI3K inhibitors, and immunotherapies such as lenalidomide and CAR-T, which can provide a promising strategy for older patients. Herein we review the current therapies for older MCL patients, chemotherapy regimens, targeted therapies, and immunotherapies.
- |||||||||| buparlisib (AN2025) / Novartis, Adlai Nortye
Preclinical, Journal: Preclinical and clinical evaluation of Buparlisib (BKM120) in recurrent/refractory Central Nervous System Lymphoma. (Pubmed Central) - Aug 31, 2023
P2
The presence of Buparlisib in plasma and CSF was confirmed 2h post-treatment with a median CSF concentration below the EC50 defined in the cell line All four patients were evaluated for response and the median time to progression was 39?days. Buparlisib monotherapy did not lead to meaningful responses and the trial was prematurely stopped.Clinical Trial Registration: NCT02301364.
- |||||||||| dizocilpine (MK801) / Merck (MSD)
Preclinical, Journal: The Potent and Selective Histamine H3 Receptor Antagonist E169 Counteracts Cognitive Deficits and Mitigates Disturbances in the PI3K/AKT/GSK-3? Signaling Pathway in MK801-Induced Amnesia in Mice. (Pubmed Central) - Aug 30, 2023
Moreover, the results observed revealed that E169 (2.5-10 mg/kg, i.p.) did not alter anxiety levels and locomotor activity of animals in open field tests, demonstrating that performances improved following acute systemic administration with E169 in NORT are unrelated to changes in emotional response or in spontaneous locomotor activity. In summary, these obtained results suggest the potential of H3R antagonists such as E169, with good in silico physicochemical properties and stable retained key interactions in docking studies at H3R, in simultaneously modulating disturbed brain neurotransmitters and the imbalanced Akt-mTOR signaling pathway related to neurodegenerative disorders, e.g., AD.
- |||||||||| MEN1611 / Menarini
Enrollment change, Metastases: MEN1611 With Cetuximab in Metastatic Colorectal Cancer (C-PRECISE-01) (clinicaltrials.gov) - Aug 30, 2023
P1/2, N=29, Active, not recruiting,
This discovery provided experimental support for constituting a promising strategy for T-cell acute lymphoblastic leukemia (T-ALL) therapy. N=42 --> 29
- |||||||||| Piqray (alpelisib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene, buparlisib (AN2025) / Novartis, Adlai Nortye
The combination of PI3Ki and MEKi: a promising treatment option especially for BRAF wild-type melanoma patients (e-Poster Hall) - Aug 30, 2023 - Abstract #EADV2023EADV_3243;
As monotherapy, the pan-PI3K inhibitor BKM120 can induce growth inhibition and apoptosis in most of the melanoma models tested, but shows severe side effects in patients...Initial in ovo test results (on chick chorioallantoic membrane (CAM)) showed reduced tumor burden by using BYL719 in combination with the MEKi trametinib. These data suggest that the combination of PI3Ki with MEKi may be a new therapeutic option for BRAF wild-type melanoma patients.
- |||||||||| Piqray (alpelisib) / Novartis
Alpelisib For PIK3CA-Related Vascular Anomaly (e-Poster Hall) - Aug 30, 2023 - Abstract #EADV2023EADV_2457;
The study of vascular birthmarks is a rapidly evolving area of medicine as our knowledge of the genetic mechanisms underpinning these lesions advances. We present one of the first patients in Australia to be treated with alpelisib and highlight the importance of multidisciplinary care foregrounding the roles of dermatology, pathology, and genetics in the management of this case.
- |||||||||| Erbitux (cetuximab) / Eli Lilly, EMD Serono
Biomarker, Journal: Mutant PIK3CA as a negative predictive biomarker for treatment with a highly selective PIM1 inhibitor in human colon cancer. (Pubmed Central) - Aug 29, 2023
Significant improvement in targeted therapy for colorectal cancer (CRC) has occurred over the past few decades since the approval of the EGFR inhibitor cetuximab...Inhibition of PIK3CA MT by PI3K inhibitors restored SMI-4a sensitivity in PIK3CA MT CRC cell lines. Taken together, these results demonstrate that sensitivity to SMI-4a is determined by the PIK3CA genotype and that co-targeting of PI3K and PIM1 in PIK3CA MT CRC patients could be a promising and novel therapeutic approach for refractory CRC patients.
- |||||||||| LY294002 / Eli Lilly
Journal: Inhibition of the interaction between Hippo/YAP and Akt signaling with ursolic acid and 3'3-diindolylmethane suppresses esophageal cancer tumorigenesis. (Pubmed Central) - Aug 29, 2023
Moreover, the addition of the Akt inhibitor LY294002 and the PI3K inhibitor 3-methyladenine enhanced the inhibitory effects of UA plus DIM on Akt pathway activation and further stimulated the Hippo pathway, including the suppression of YAP nuclear translocation in esophageal cancer cells...Furthermore, in a xenograft nude mice model, UA plus DIM treatment effectively diminished esophageal tumors by inactivating the Akt pathway and stimulating the Hippo signaling pathway. Thus, our study highlights a feedback loop between the PI3K/Akt and Hippo signaling pathways in esophageal cancer cells, implying that a low dose of UA plus DIM could serve as a promising chemotherapeutic combination strategy in the treatment of esophageal cancer.
- |||||||||| Journal, IO biomarker: Current Treatments in Mantle Cell Lymphoma. (Pubmed Central) - Aug 28, 2023
Also promising are antibody-drug conjugates such as ROR1 inhibitors and PI3K inhibitors, which are under clinical investigation. We provide an overview of the molecular mutations identified in MCL and the evolving treatment strategies for this disease.
- |||||||||| Journal: Trichomonas gallinae Kills Host Cells Using Trogocytosis. (Pubmed Central) - Aug 25, 2023
To the best of our knowledge, our study has demonstrated for the first time that T. gallinae uses trogocytosis to kill host cells. Understanding this mechanism is crucial for the prevention and control of avian trichomoniasis and will contribute to the development of vaccines and drugs for the prevention and control of avian trichomoniasis.
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