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67 Companies | 59 Products |
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344 Diseases | |
342 Trials |  |
12240 News |  |
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- Venclexta (venetoclax) / Roche, AbbVie
Identifying Mechanisms Associated with Venetoclax Resistance in Multiple Myeloma (MM) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4308;
Our study also indicates that upstream signaling involved in BCL2 family regulation during acquired resistance is likely related to cytokine, growth factor, and/or RTK–induced cell signaling such as PI3K. Co-inhibition of MCL-1, or BCLXL, as well as the upstream PI3K, RTK (FGF and EGF), IGF-1 mediated signaling were effective in overcoming VTX resistance.
- Campath (alemtuzumab) / Sanofi
Real-World Evidence on Therapeutic Strategies and Treatment-Sequencing in Patients with Chronic Lymphocytic Leukemia: An International Study of Eric, the European Research Initiative on CLL (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4274;
Regarding novel targeted agents, 1860/9173 (20.2%) patients had received at least one line of treatment with BTKi (ibrutinib, n=1788; acalabrutinib, n=72) over the disease course; 631/9173 (6.9%) with venetoclax; and, 447/9173 (4.9%) with the PI3K inhibitor idelalisib...The great majority (865/1086 cases, 79.7%) of patients who received a second line before 2014 were retreated with CIT, most commonly Bendamustine-Rituximab (284/1086, 26.1%) and Fludarabine-Cyclophosphamide-Rituximab (252/1086, 23.2%); alemtuzumab monotherapy was used in 55/1086 (5%) of patients...Patients treated with CIT (n=694) had an ORR of 68.7% (28.3% CR+40.4% PR). In conclusion, in a large international study we provide real world data regarding the selection and sequencing of treatment in CLL, charting a major shift in treatment patterns before and after the Introduction of novel trargeted agents and confirming their efficacy even in high-risk CLL.
- Outcomes of Chronic Lymphocytic Leukemia and Richter Transformation Following Discontinuation of Non-Covalent Bruton’s Tyrosine Kinase Inhibitors (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4268;
For venetoclax naive CLL pts, venetoclax appears to be a promising strategy following ncBTKi discontinuation supporting the ability to stay within the BTKi class prior to switching to venetoclax. Cellular therapies including CAR T-cell therapy and allo SCT had a high ORR and warrant further investigation (80% of pts had prior cBTKi, ncBTKi and venetoclax and 100% had prior cBTKi and ncBTKi).
- Venclexta (venetoclax) / Roche, AbbVie
Addressing a New Challenge in Chronic Lymphocytic Leukemia: Outcomes of Therapies after Exposure to Both a Covalent Bruton’s Tyrosine Kinase Inhibitor and Venetoclax (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4267;
Practice patterns are variable and no standard of care exists for CLL pts previously treated with a cBTKi and ven. Additionally, approved standard therapies including CIT combinations and PI3Kis yield poor outcomes with responses which are not durable.
- Jakafi oral (ruxolitinib) / Novartis, Incyte, parsaclisib (INCB50465) / Incyte
A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of Ruxolitinib Plus Parsaclisib in Patients with JAK- and PI3K-Inhibitor Treatment–Naive Myelofibrosis (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4214;
P3
Secondary objectives include evaluation and comparison of patient-reported MF symptoms, overall survival, time to onset and duration of response in spleen volume, and safety and tolerability of ruxolitinib plus parsaclisib vs ruxolitinib plus placebo. Sites are open across the United States, Europe, United Kingdom, and Asia.
- Spikevax (elasomeran) / Moderna, Takeda
Immunogenicity of Sars-Cov-2 mRNA 1273 Vaccine in Patients with Lymphoid Malignancies (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_4136;
Current or past treatments with CD20 mAb/BTKi/PI3Ki/venetoclax and CAR-T were associated with lower immune response, with pooled SV rates of 16.7% after 2 doses. In general, LM pts had lower SV rates and Ab titers after the 1 st dose vs ST, but responses improved after the 2 nd dose.
- Zydelig (idelalisib) / Gilead
Pharmacological Targeting of PI3K-Dependent Central Tolerance Mechanisms in Refractory Pre-Germinal Center B-Cell Malignancies (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3886;
While designed to eliminate autoreactive clones during early B-cell development, we recently discovered that B-ALL, MCL and U-CLL fully retained sensitivity to central tolerance mechanisms, which are triggered by persistent PI3K-hyperactivation. PI3K-signaling code to distinguish between normal and pathological signaling.
- SRX3177 / SignalRx
The Novel Multitarget Small-Molecule Inhibitor SRX3177 Overcomes Ibrutinib Resistance in Mantle Cell Lymphoma (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3881;
Although there is no defined standard of care for MCL treatment, some combination of chemo-immunotherapy and rituximab maintenance with or without autologous stem cell transplantation is generally employed depending on the age and fitness of the patient...Further, we show that SRX3177 is more potent to tumor cells than the individual PI3K (BKM120), BTK (Ibrutinib), BRD4 (JQ1), and CDK4/6 (palbociclib) inhibitors, and dual PI3K/BRD4 inhibitor SF2523 (backbone for SRX3177) in JeKo-1 cells...Hence, the triple inhibitor SRX3177 has superior potency to ibrutinib in MCL cell lines and succeeds in overcoming ibrutinib-resistance at nanomolar doses. Taken together, our data supports the development of SRX3177 as a novel therapeutic agent for treatment of MCL.
- Aliqopa (copanlisib) / Bayer, Verzenio (abemaciclib) / Eli Lilly
Abemaciclib in Combination with Copanlisib to Overcome Therapeutic Resistance in Mantle Cell Lymphoma (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3872;
Taken together, these results suggest that the combinatory therapy is effective in overcoming venetoclax resistance in MCL. Conclusions Combinatory treatment with abemaciclib and copanlisib may achieve clinical actionable efficacy through overcoming the venetoclax-resistance in MCL that may become an effective treatment regimen for refractory/relapsed MCL patients in the future.
- Healthcare Resource Utilization and Costs of Patients with Relapsed/Refractory Follicular Lymphoma Receiving 3 or More Lines of Therapy (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3518;
More than 40% of the pts in this analysis needed subsequent treatment, further compounding the challenges faced by this high-risk population. This analysis provides an initial benchmark for ongoing and future evaluations of the economic value of currently available and emerging therapies for multiple relapsed FL, though future studies with larger sample sizes and longer follow-up are warranted.
- lenalidomide / Generic mfg.
Variance in Practice between Experts and Oncology Healthcare Professionals for Follicular Lymphoma: Analysis of an Online Treatment Decision Tool (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3517;
A majority of HCPs who initially selected treatment options that diverged from expert recommendations or who were uncertain about treatment choice changed their intended therapy to match the experts, suggesting that this online decision support tool may increase the number of HCPs making optimal management decisions for patients with FL. Detailed comparisons of expert recommendations and HCP responses from the online tool will be presented.
- pictilisib (GDC-0941) / Roche
Targeting PI3K-AKT-mTOR Signaling in Multiple Myeloma Mesenchymal Stem Cells Mediates Antiproliferative Effect on Myeloma Cells (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3179;
Various functional assays for proliferation, apoptosis and cell cycle were performed either using a mono-culture or co-culture protocol of MSC and the MM-cell lines MM.1S and SKMM2 treating the cells with the pan-PI3K-inhibitor GDC-0941...Our data further provides a deeper insight into the molecular signature of MM-MSCs, a predictive of patient prognosis and treatment outcome. Targeting MSCs as a crucial part of the MM-BM niche by using PI3K-inhibitors could contribute to novel therapeutic strategies to effectively block MM-MSC interaction improving overall patient survival.
- Venclexta (venetoclax) / Roche, AbbVie
Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Treated with the Combination of Ibrutinib (I) and Venetoclax (V; I+V) after Progression on I Alone (V-naïve) or after Progression on Sequential I and V (Double-Refractory) (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3138;
Next therapy (n=9) consisted of Richter transformation treatment (n=2), chemotherapy plus continued I+V (n=1), anti-CD20 plus continued I+V (n=1), duvelisib + I (n=1), TP-0903 + I (n=1), reIntroduction of I at disease progression after previously stopping I during I+V therapy (n=1), and reIntroduction of I (n=1) or V (n=1) at disease progression after previously stopping I+V...Eight pts required additional treatment, consisting of PI3K inhibitor (n=2), anti-CD20 added to I+V (n=1), CAR-T (n=1), anti-CD20 with (n=1) or without (n=1) bendamustine added to continued I, and Richter transformation treatment (n=2)...In the double-refractory setting, repurposing both drugs as combination I+V therapy can be a useful strategy, despite the short-term disease control, for pts where clinical trial options are limited or not available. Further examination of these approaches in larger cohorts and understanding the operative resistance mechanisms in pts with double-refractory disease are key next studies.
- Jakafi oral (ruxolitinib) / Novartis, Incyte, parsaclisib (INCB50465) / Incyte
A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Add-on Parsaclisib in Patients with Myelofibrosis Who Have Suboptimal Response to Ruxolitinib (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3076;
P3
Secondary objectives are to evaluate and compare the effect of add-on parsaclisib vs placebo on patient-reported MF symptoms, overall survival, time to onset and duration of spleen volume response, and safety and tolerability. Sites are open throughout North America, Europe, and Asia.
- sirolimus / Generic mfg.
Deciphering the Mechanisms of Osteoblast-Induced Resistance of Leukemic Stem Cell (LSC) in Ph+ CML: Role of PI3-Kinase, BRD4 and MYC and Development of Strategies to Overcome Osteoblast-Induced Resistance (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3054;
We found that the dual PI3 kinase (PI3K) and mTOR inhibitor BEZ235 and the selective pan-PI3K inhibitor copanlisib suppress proliferation of primary osteoblasts (BEZ235 IC 50 : 0.05 µM; copanlisib IC 50 : 0.05 µM), the osteoblastic cell line CAL-72 (BEZ235 IC 50 : 0.5 µM; copanlisib IC 50 : 1 µM), primary human umbilical vein endothelial cells (BEZ235 IC 50 : 0.5 µM; copanlisib IC 50 : 0.5 µM) and the endothelial cell line HMEC-1 (BEZ235 IC 50 : 1 µM; copanlisib IC 50 : 1 µM), whereas no comparable effects were seen with the mTOR inhibitor rapamycin...Furthermore, BEZ235 and copanlisib were found to overcome osteoblast-induced resistance of K562, KU812 cells, and primary CD34 + /CD38 − CML LSC against nilotinib and ponatinib...Of all other drugs tested, only the BRD4-targeting drug JQ1 was found to suppress CAL72-induced resistance in the CML cell lines KU812 and K562, suggesting that osteoblast-induced resistance of CML cells is also mediated by a BRD4-MYC pathway...In conclusion, our data show that osteoblast-induced resistance of CML stem cells is mediated by a PI3K-dependent pathway and BRD4/MYC, and that BRD4-inhibition or BRD4-degradation counteracts osteoblast-induced resistance of CML (stem) cells against BCR-ABL1 inhibitors and PD-L1 expression on CML LSC and osteoblasts. We hypothesize that checkpoint inhibition may assist in drug-induced eradication of CML LSC and thus in the development of curative drug therapies in Ph + CML.
- ifosfamide / Generic mfg.
Novel Single Agents Are Equivalent to Conventional Chemotherapy Inpatients with Relapsed and Refractory Mature T-Cell Lymphomas: A Meta-Analysis (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_3002;
These findings warrant serious consideration in the design and development of clinical trials for patients with R/R PTCL and the need for tailored treatments. Our meta-analysis also informs clinicians and patients about the benefits of single agents in comparison with standard chemotherapy while making clinical decisions for specified histologies.
- parsaclisib (INCB50465) / Incyte, Rituxan (rituximab) / Biogen, Zenyaku Kogyo, Roche
Parsaclisib in Combination with R-CHOP for Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma: Preliminary Results of a Phase 1/1b Study (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2985;
P1
The preliminary efficacy signal of objective response appears encouraging in a small cohort of high risk patients. Parsaclisib plus R-CHOP can be an experimental arm for future frontline DLBCL trials investigating genetic subtype-driven novel therapies.
- linperlisib (YY-20394) / Shanghai YingLi Pharma
A Phase Ib Study of Linperlisib in Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2955;
P1
Conclusions The PI3Kd-selective oral agent, linperlisib, demonstrated promising efficacy and durable responses with a 61.0% ORR and 10.3 months median PFS in patients with r/r PTCL. Additional clinical studies of linperlisib in r/r PTCL, including a Phase 2 registration study, are currently ongoing.
- buparlisib (BKM120) / Novartis, Adlai Nortye
Targeting Metabolic Vulnerabilities in Primary Effusion Lymphoma Using the Novel Nucleoside Analog 6-Eti (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2747;
Our data indicates that ADK KO cells have undergone metabolic reprogramming to upregulate de novo pyrimidine biosynthesis and p70S6K signaling. Moreover, we found that 6-ETI synergizes with the pan PI3K inhibitor BKM120 highlighting nucleotide metabolism and PI3K/mTOR signaling as key therapeutic vulnerabilities targeted by this novel nucleoside analog.
- Thrombin-Induced Oxidative Phosphorylation in Platelets Is Repressed By Dengue Virus through Inhibition of the PI3K/Akt Signaling Pathway (GWCC - Hall B5, Level 1) - Nov 5, 2021 - Abstract #ASH2021ASH_2552;
Dengue virus inhibits thrombin-induced phosphorylation at different levels in the platelet. First, by reducing the expression of the GPIb molecule on the platelet surface.
- parsaclisib (INCB50465) / Incyte
Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Follicular Lymphoma: Primary Analysis from a Phase 2 Study (CITADEL-203) (GWCC - Sidney Marcus Auditorium, Level 4) - Nov 5, 2021 - Abstract #ASH2021ASH_2320;
P2
Parsaclisib monotherapy demonstrated a rapid and durable response, had an acceptable safety profile, and was generally well tolerated in pts with R/R FL. These data suggest that parsaclisib could be a favorable treatment option for pts with R/R FL.
- Actemra IV (tocilizumab) / Roche, JW Pharma
Updated Clinical and Correlative Results from the Phase I CRB-402 Study of the BCMA-Targeted CAR T Cell Therapy bb21217 in Patients with Relapsed and Refractory Multiple Myeloma (GWCC - Hall C2-C3) - Nov 5, 2021 - Abstract #ASH2021ASH_1986;
P1
Efficacy results are encouraging with a median DOR estimate of 17M, CR rate continues to mature. Patients with higher levels of proliferative, less differentiated memory like CAR+ T cells at peak expansion are more likely to experience prolonged DOR, continuing to support the hypothesis that the memory like T cell phenotype associated with bb21217 results in prolonged DOR.
- pirtobrutinib (LOXO-305) / Eli Lilly
Pirtobrutinib, A Next Generation, Highly Selective, Non-Covalent BTK Inhibitor in Previously Treated CLL/SLL: Updated Results from the Phase 1/2 BRUIN Study (GWCC - B401-B402, Level 4) - Nov 5, 2021 - Abstract #ASH2021ASH_1763;
P1/2
Pirtobrutinib was well tolerated and exhibited a wide therapeutic index. Updated data, including approximately 100 new pts with CLL and an additional 10 months since the prior data cut will be presented.
- parsaclisib (INCB50465) / Incyte
Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Mantle Cell Lymphoma Not Previously Treated with a BTK Inhibitor: Primary Analysis from a Phase 2 Study (CITADEL-205) (GWCC - Thomas Murphy Ballroom 1-2, Level 5) - Nov 5, 2021 - Abstract #ASH2021ASH_1752;
P2
Parsaclisib monotherapy demonstrated a rapid and durable response, had an acceptable safety profile, and was generally well tolerated in BTK inhibitor–naive pts with R/R MCL. These data suggest that parsaclisib could be a potential treatment option for pts with R/R MCL.
- daporinad (APO866) / Onxeo, OT-82 / OncoTartis, Copiktra (duvelisib) / Secura Bio, Yakult Honsha
Evidence of a Synergistic Cross-Talk between the B Cell Receptor (BCR) and Nicotinamide Phosphoribosyl Transferase (NAMPT) in Richter’s Syndrome Patient-Derived Xenograft Models: Therapeutic Implications (GWCC - Thomas Murphy Ballroom 3-4, Level 5) - Nov 5, 2021 - Abstract #ASH2021ASH_1560;
As NAMPT inhibitors (NAMPTi) we used both FK866 and OT-82, which are validated small molecules. These results highlight a crosstalk between BCR signalling and NAMPT/sirtuin axis in RS models, showing the increased efficacy of the dual targeting (i.e., PI3K-δ/γ and NAMPT), and supporting this novel and promising therapeutic strategy for the treatment of RS patients.
- ibrutinib / Generic mfg.
Chronic Lymphocytic Leukemia Cells with Mutated Nfkbie Are Positively Selected By Microenvironmental Signals and Display Reduced Sensitivity to Ibrutinib Treatment (GWCC - Thomas Murphy Ballroom 3-4, Level 5) - Nov 5, 2021 - Abstract #ASH2021ASH_1558;
In contrast to IBR, both drugs inhibited the proliferation of NFKBIE-mutated cells in vitro , with a greater effect observed with idelalisib. Collectively, these data demonstrate that NFKBIE mutations can reduce the response to IBR treatment and suggest that such cases may benefit more from treatment with a PI3K inhibitor.
- Actemra IV (tocilizumab) / Roche, JW Pharma, mosunetuzumab (BTCT4465A) / Roche
Mosunetuzumab Monotherapy Is an Effective and Well-Tolerated Treatment Option for Patients with Relapsed/Refractory (R/R) Follicular Lymphoma (FL) Who Have Received ≥2 Prior Lines of Therapy: Pivotal Results from a Phase I/II Study (GWCC - Thomas Murphy Ballroom 1-2, Level 5) - Nov 5, 2021 - Abstract #ASH2021ASH_1406;
P1/2
High response rates are achieved (ORR: 78.9%; CR: 57.8%) and maintained for ≥12 months in the majority of pts. Mosun has a manageable safety profile, with C1 step-up dosing effectively mitigating CRS, enabling treatment without mandatory hospitalization.
- imatinib / Generic mfg.
The Sustainability of Price Dynamics in Precision Hematology (GWCC - B207-B208, Level 2) - Nov 5, 2021 - Abstract #ASH2021ASH_1334;
For non-generic BCR-ABLi and anti-CD20 antibodies, despite there being several agents, the rise in drug expenditures correlated closely, calling into question the true value of within-class competition. There is an urgent need for drug pricing reform given the average expenditure of Medicare part D, and ultimately out-of-pocket costs for our patients with cancer continues to trend upwards.
- Ukoniq (umbralisib) / TG Therap, Utuxin (ublituximab) / TG Therap
The Combination of Umbralisib Plus Ublituximab Is Active in Patients with Relapsed or Refractory Marginal Zone Lymphoma (MZL): Results from the Phase 2 Global Unity-NHL Trial (GWCC - A411-A412, Level 4) - Nov 5, 2021 - Abstract #ASH2021ASH_1254;
P2b
U2 was highly active in patients with R/R MZL, with improved efficacy when compared to a prior cohort of MZL patients treated in this study with umbra mono (Fowler JCO 2021). The safety profile of the U2 combination was manageable, with a relatively low incidence of immune-mediated toxicities and AE-related discontinuations.
- parsaclisib (INCB50465) / Incyte
Efficacy and Safety of Parsaclisib in Patients with Relapsed or Refractory Marginal Zone Lymphoma: Primary Analysis from a Phase 2 Study (CITADEL-204) (GWCC - A411-A412, Level 4) - Nov 5, 2021 - Abstract #ASH2021ASH_1253;
P2
Treatment was generally well tolerated, and the safety profile was manageable. Results suggest parsaclisib may be a potential treatment option for R/R MZL.
- | Journal: ELABELA improvesendothelial cell function via the ELA-APJ axis by activating the PI3K/Akt-signaling pathway in HUVECs and EA.hy926 cells. (Pubmed Central) - Nov 5, 2021
Further verification tests were performed using the PI3K inhibitor wortmannin, and the results illustrated that inhibiting PI3K/Akt signaling blocked the positive effects of ELA on EC function and APJ receptor expression. Taken together, our findings indicate that ELA may alter EC function via the ELA-APJ axis and PI3K/Akt signaling and thatELA shows promise for usein endothelial dysfunction therapy for preventing and treating PE.
- | Journal: LncRNA RHPN1-AS1 Promotes Cell Proliferation, Migration and Invasion Through Targeting miR-7-5p and Activating PI3K/AKT/mTOR Pathway in Hepatocellular Carcinoma. (Pubmed Central) - Nov 5, 2021
Moreover, silencing lncRNA RHPN1-AS1 also inhibited the activation of PI3K/AKT/mTOR pathway. Taken together our findings demonstrated that lncRNA RHPN1-AS1 could facilitate cell proliferation, migration and invasion via targeting miR-7-5p and activating PI3K/AKT/mTOR pathway in HCC.
- | Journal: Silencing of SPP1 Suppresses Progression of Tongue Cancer by Mediating the PI3K/Akt Signaling Pathway. (Pubmed Central) - Nov 5, 2021
Compared with normal SCC154 cells and Si-RNA control SCC154 cells, the expressions of Phosphatidylinositol 3-kinase/Akt pathway proteins in si-SPP1 SCC154 cells were significantly decreased (*P < 0.05), and the protein activities and proliferation abilities were also significantly decreased (*P < 0.05), while the migration ability, invasion ability, and cancer forming ability were significantly increased (*P < 0.05). Inhibition of the SPP1 gene may have a therapeutic effect on tongue cancer, and could be an effective target for the treatment of this disorder.
- | Preclinical, Journal, IO biomarker: Cangfudaotan Decoction Alleviates Insulin Resistance and Improves Follicular Development in Rats with Polycystic Ovary Syndrome via IGF-1-PI3K/Akt-Bax/Bcl-2 Pathway. (Pubmed Central) - Nov 5, 2021
Further experiments suggested that CDF improves IR, follicular development, cell apoptosis, and inflammatory microenvironment, and this was associated to the regulation of IGF-1-PI3K/Akt-Bax/Bcl-2 pathway-mediated gene expression. Given that CFD sufficiently suppresses insulin resistance and improves follicular development in this study, exploring these mechanisms might help to optimize the therapeutic treatment of CFD in PCOS patients.
- | Journal, IO biomarker: Diallyl trisulfide regulates cell apoptosis and invasion in human Osteosarcoma U2OS cells through regulating PI3K/AKT/GSK3β signaling pathway. (Pubmed Central) - Nov 5, 2021
Therefore, our data demonstrated that DATS exerted its anticancer effects by inhibiting cell proliferation, migration and invasion in vitro and in vivo. These results provide evidence for the use of the natural product DATS either alone or in combination with standard therapy for OS.
- | Journal: Kaiso regulates osteoblast differentiation and mineralization via the Itga10/PI3K/AKT signaling pathway. (Pubmed Central) - Nov 5, 2021
Moreover, integrin subunit α10 (Itga10) was identified as a direct target of Kaiso via chromatin immunoprecipitation and luciferase reporter assays. Collectively, these findings suggested that Kaiso regulated the differentiation of osteoblasts via the Itga10/PI3K/AKT pathway, which represents a therapeutic target for bone formation or bone resorption‑related diseases.
- | metformin / Generic mfg.
Preclinical, Journal: Effect of Inonotus obliquus (Fr.) Pilat extract on the regulation of glycolipid metabolism via PI3K/Akt and AMPK/ACC pathways in mice. (Pubmed Central) - Nov 5, 2021
obliquus extract ameliorated insulin resistance and lipid metabolism disorders in diabetic mice. The hypoglycemic and hypolipidemic properties of I. obliquus extract were supposedly exerted via the regulation of the PI3K/Akt and AMPK/ACC signaling pathways.
- | Venclexta (venetoclax) / Roche, AbbVie, quercetin (LY294002) / Eli Lilly
Journal, IO biomarker: Synergistic effects of LY294002 and ABT199 on the cell cycle in K562, HL60 and KG1a cells. (Pubmed Central) - Nov 5, 2021
At the molecular level, LY294002 and ABT199 combination treatment significantly downregulated Skp2, Bcl2, procaspase‑3 and procaspase‑9 expression levels, but markedly upregulated p27, Bax, cleaved caspase‑3 and caspase‑9 expression levels in K562, HL‑60 and KG1a cells. The results of the present study demonstrated that LY294002 and ABT199 combination treatment may serve as a novel therapeutic strategy for AML.
- | Journal: SRY-Box 21 Antisense RNA 1 Knockdown Diminishes Amyloid Beta-Induced Neuronal Damage by miR-132/PI3K/AKT Pathway. (Pubmed Central) - Nov 5, 2021
The PI3K/AKT signaling was repressed in Aβ-challenged cells, but this effect was counteracted upon overexpression of miR-132. In conclusion, SOX21-AS1 knockdown mitigated Aβ-dependent neuronal cell damage by promoting miR-132/PI3K/AKT pathway.
- | Journal: Methyl-CpG-Binding Domain Protein 3 Promotes Seizures by Recruiting Methyltransferase DNMT1 to Enhance TREM2 Methylation. (Pubmed Central) - Nov 5, 2021
Inhibition of MBD3 reduced the level of epileptic seizures, down-regulated cg25748868 methylation, activated TREM2-mediated signaling pathways, and alleviated hippocampal neuronal damage in the acute seizure mouse models. The present study unveiled that MBD3 and DNMT1 synergistically enhanced hypermethylation of cg25748868 in TREM2, and promoted the onset of epilepsy via inhibition of the PI3K/Akt pathway.
- | Preclinical, Journal: Huiyang Shengji decoction promotes wound healing in diabetic mice by activating the EGFR/PI3K/ATK pathway. (Pubmed Central) - Nov 5, 2021
HYSJD promotes the proliferation of epidermal cells in chronic diabetic wounds by increasing EGFR expression in the wounds and activating the PI3K/AKT signaling pathway. Our study provides an experimental basis for the pharmacological mechanism of HYSJD.
- | Journal: Exosome miR-134-5p restrains breast cancer progression via regulating PI3K/AKT pathway by targeting ARHGAP1. (Pubmed Central) - Nov 5, 2021
Our study provides an experimental basis for the pharmacological mechanism of HYSJD. Exosome miR-134-5p restrained BC progression through regulating ARHGAP1/PI3K/AKT signaling pathway, suggesting that miR-134-5p might be a therapeutic target for BC.
- | Journal: Eupafolin induces apoptosis and autophagy of breast cancer cells through PI3K/AKT, MAPKs and NF-κB signaling pathways. (Pubmed Central) - Nov 5, 2021
Moreover, Eupafolin treatment significantly weakened carcinogenesis of MCF-7 cells in nude mice. Therefore, this data provides novel directions on the use of Eupafolin for treatment of breast cancer.
- | Journal: Hey1 promotes migration and invasion of melanoma cells via GRB2/PI3K/AKT signaling cascade. (Pubmed Central) - Nov 5, 2021
In summary, our results suggest that Hey1 promotes the invasion and metastasis of melanoma cells by regulating GRB2/PI3K/AKT pathway. Our study provides potential therapeutics in tumor biology.
- ||||||| Copiktra (duvelisib) / Secura Bio, Yakult Honsha
Cytokine storm, Cytokine release syndrome: Just saw this patent update on Duvelisib (Pi3k) in #CytokineReleaseSyndrome #CytokineStorm #COVID19 NCT04372602 (Twitter) - Nov 4, 2021
P2
- | Journal: Blocking EGFR palmitoylation suppresses PI3K signaling and mutant KRAS lung tumorigenesis. (Pubmed Central) - Nov 4, 2021
These findings suggest a mechanism whereby oncogenic KRAS saturates signaling through unpalmitoylated EGFR, reducing formation of the PI3K signaling complex. Future development of DHHC20 inhibitors to reduce EGFR-PI3K signaling could be beneficial to patients with KRAS-mutant tumors.
- || paclitaxel / Generic mfg., fulvestrant / Generic mfg., capivasertib (AZD5363) / Otsuka, AstraZeneca
Clinical, Journal: Genetic alterations in the PI3K/AKT pathway and baseline AKT activity define AKT inhibitor sensitivity in breast cancer patient-derived xenografts. (Pubmed Central) - Nov 4, 2021
Future development of DHHC20 inhibitors to reduce EGFR-PI3K signaling could be beneficial to patients with KRAS-mutant tumors. This study provides insight into putative predictive biomarkers of response and acquired resistance to AZD5363 in HER2-negative metastatic breast cancer.
- | sirolimus / Generic mfg.
Journal: A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration. (Pubmed Central) - Nov 4, 2021
Inhibiting mTOR with rapamycin suppressed the growth of subcutaneous MET-mutant cell grafts in mice, including that of MET inhibitor-resistant cells. These findings reveal a GTPase-independent role for Rac1 in mediating a PI3K-independent MET-to-mTOR pathway and suggest alternative or combined strategies that might overcome resistance to RTK inhibitors in patients with cancer.
- | Journal: Inhibition of histamine receptor H3 suppresses the growth and metastasis of human non-small cell lung cancer cells via inhibiting PI3K/Akt/mTOR and MEK/ERK signaling pathways and blocking EMT. (Pubmed Central) - Nov 4, 2021
In nude mice bearing H1975 cell xenograft or A549 cell xenograft, administration of CPX (3 mg/kg every other day, intraperitoneal) significantly inhibited the tumor growth with increased E-cadherin and ZO-1 expression and decreased Fibronectin expression in tumor tissue. In conclusion, this study reveals that Hrh3 plays an important role in the growth and metastasis of NSCLC; it might be a potential therapeutic target against the lung cancer.
- | Journal: Selenium supplementation protects against oxidative stress-induced cardiomyocyte cell cycle arrest through activation of PI3K/AKT. (Pubmed Central) - Nov 4, 2021
We concluded that the cardioprotective effects of selenium supplementation against oxidative stress-induced cell cycle arrest in cardiomyocytes might be mediated by the selenoprotein-associated (GPx and TXNRD) antioxidant capacity, thereby activating redox status-associated PI3K/AKT pathways, which promote cell cycle progression by targeting the G2/M phase inhibitory system. This study provides new insight into the underlying mechanisms of cardioprotection effects of selenium at the cellular level.