- |||||||||| LY294002 / Eli Lilly
Journal: Titanium Dioxide Nanoparticles Induce Cell Cycle Arrest and (Pubmed Central) - Jul 16, 2024 However, LY294002 aggravated the G0/G1 phase arrest and apoptosis resulting from TiO NPs. Collectively, TiO NPs induced cell cycle arrest at G0/G1 phase and apoptosis through inhibiting the activation of PI3K/AKT/mTOR pathway, which could be the main reason for the reduction in sperm numbers caused by TiO NPs.
- |||||||||| Piqray (alpelisib) / Novartis, Truqap (capivasertib) / Otsuka, AstraZeneca
Biomarker, Review, Journal: Navigating the Complexity of PI3K/AKT Pathway in HER-2 Negative Breast Cancer: Biomarkers and Beyond. (Pubmed Central) - Jul 15, 2024 We have summarised the clinical data on the approved and discontinued agents targeting this pathway and have assessed the drugs development, successes, and failures. Finally, because of tumour heterogeneity, we emphasise the importance of reassessing the mutational status of PI3KCA in both metastatic tissue and blood at the time of disease progression to better tailor treatment for patients.
- |||||||||| Review, Journal: Unraveling the noncoding RNA landscape in glioblastoma: from pathogenesis to precision therapeutics. (Pubmed Central) - Jul 15, 2024
Targeting oncogenic ncRNAs with RNA-interfering strategies such as MOs, ASOs, LNAs, CRISPR-Cas9 gene editing, and PNA approaches may represent a promising therapeutic strategy for GBM. This review emphasizes the critical role of ncRNAs in GBM pathogenesis, as well as the potential for new therapeutic strategies targeting these pathways to improve the prognosis and quality of life for GBM patients.
- |||||||||| Piqray (alpelisib) / Novartis
Journal: Influenza A defective viral genomes and non-infectious particles are increased by host PI3K inhibition via anti-cancer drug alpelisib. (Pubmed Central) - Jul 15, 2024 In sum, we provide evidence that host cell metabolism can increase the production of defective viral genomes and particles at an early stage of infection, shifting the makeup of the infection and potential interactions among virions. Given that Influenza A defective viral genomes can inhibit pathogenesis, our study presents a new line of investigation into metabolic states associated with less severe flu infection and the potential induction of these states with metabolic drugs.
- |||||||||| Piqray (alpelisib) / Novartis, Mekinist (trametinib) / Novartis, BeiGene, buparlisib (AN2025) / Adlai Nortye
The combination of PI3Ki (phosphatidylinositol-3-kinase inhibitor) and MEKi (mitogen-activated protein kinase inhibitor) as a promising treatment option for melanoma patients with NRAS-mutated tumors. (Room 12) - Jul 11, 2024 - Abstract #ADO2024ADO_519; In monotherapy, the pan-PI3K inhibitor BKM120 (activity against p110 alpha, beta, gamma, and delta isoforms) is able to induce growth inhibition and apoptosis in most of the melanoma models tested to date, whereas BYL719, an alpha-specific inhibitor, has limited antitumor activity as monotherapy...Initial in vivo test results (in ovo) on chick chorioallantoic membrane (CAM) showed reduced tumor burden and micrometastases by using the p110alpha-specific BYL719 in combination with trametinib...These data show that the combination of PI3K inhibitors with MEK inhibitors could be a new therapeutic option for melanoma patients. By using PI3K?-selective inhibitors, potential side effects could be reduced compared to pan-PI3K inhibitors.
- |||||||||| Review, Journal: Polarization of M2 Tumor-Associated Macrophages (TAMs) in Cancer Immunotherapy. (Pubmed Central) - Jul 11, 2024
Clearly, due to the distinct features of various cancers and their heterogeneities, a single approach outlined above might only be effective against some cancers and not others. In addition, targeting by itself may not be efficacious unless used in combination with other therapeutic modalities.
- |||||||||| LY294002 / Eli Lilly
Journal: CTRP6 alleviates endometrial fibrosis by regulating Smad3 pathway in intrauterine adhesion (Pubmed Central) - Jul 10, 2024 Mechanistically, CTRP6 activated the AMP-activated protein kinase (AMPK) and protein kinase B (AKT) pathway in HESCs, and AMPK inhibitor (AraA) or PI3K inhibitor (LY294002) pretreatment abolished the protective effect of CTRP6 on TGF-?1-induced fibrosis...Therefore, CTRP6 ameliorates endometrial fibrosis, among which AMPK and AKT are essential for the anti-fibrotic effect of CTRP6 via the Smad3 pathway. Taken together, CTRP6 may be a potential therapeutic target for the treatment of intrauterine adhesion.
- |||||||||| Journal: HER3 V104 mutations regulate cell signaling, growth, and drug sensitivity in cancer. (Pubmed Central) - Jul 9, 2024
COS7 cells transiently transfected with the HER3-V104L mutation in the presence of HER binding partners showed higher expression of p-HER3, p-ERK1/2 versus HER3-WT in a NRG-independent manner without any change in AKT signaling. Overall, this study shows the clinical relevance of the HER3 V104L and the V104M mutations and its response to HER2, PI3K and ERK inhibitors.
- |||||||||| bleomycin / Generic mfg.
Journal: Fibroblast growth factor 21 alleviates idiopathic pulmonary fibrosis by inhibiting PI3K-AKT-mTOR signaling and stimulating autophagy. (Pubmed Central) - Jul 6, 2024 We administered FGF21 to bleomycin (BLM)-treated mice, which ameliorated their defects in lung function, reduced the accumulation of collagen, restored tissue structure, reduced the deposition of hydroxyproline, reduced the expression of collagen I and ?-SMA and increased the expression of E-cadherin...We also determined the effects of FGF21 in A549 cells treated with TGF-?, and found that FGF21 significantly inhibits activation of the AKT signaling pathway, thereby reducing TGF-?-induced EMT and preventing the uncontrolled proliferation of fibroblasts. We conclude that FGF21 ameliorates IPF by inhibiting the PI3K-AKT-mTOR signaling pathway and activating autophagy, which provides a theoretical basis for FGF21 to be used for the treatment of IPF.
- |||||||||| New Agents in Marginal Zone Lymphoma (Level 3, 370 BE) - Jul 5, 2024 - Abstract #SOHO2024SOHO_12;
P2 The median overall survival (OS) was not reached.5 The ACE-LY-003 study evaluated acalabrutinib in 43 R/R MZL patients...The CITADEL-204 study evaluated PI3Kd inhibitor parsaclisib daily dosing in 72 R/R MZL patients.8 The ORR was 58% with a CR rate of 4.2%, a median DOR of 12.2 months, and a median PFS of 16.5 months...Umbralisib, a dual PI3Kd/casein kinase 1e inhibitor, was evaluated in 69 R/R MZL patients in the UNITY-NHL study.9 The ORR was 49% with a CR of 16%, and the median DOR and median PFS were not reached...The double-blinded, randomized, placebo-controlled phase III CHRONOS-3 trial evaluated copanlisib with rituximab vs. rituximab in CD20-positive indolent NHL (iNHL)...The Zuma-5 clinical trial evaluated axicabtagene ciloleucel in R/R iNHL and included 24 patients (16%) with R/R MZL.11 In patients with MZL, the ORR was 83% with a CR rate of 65%...Bispecific antibodies targeting CD20 and CD3 that redirect T cells to engage and eliminate malignant B cells and antibody-drug conjugates, such as loncastuximab tesirine, demonstrated excellent responses in FL and aggressive NHL; however, scarce data exist for MZL...Therefore, targeting of only one aberrant signaling pathway may not be sufficient to completely eliminate the tumor. Therefore, usage of combination therapies, including bispecific antibodies and antibody-drug conjugates, may represent the next step toward the cure of MZL patients.
- |||||||||| Journal: NAT1 inhibits liver metastasis of colorectal cancer by regulating EMT and glycolysis. (Pubmed Central) - Jul 5, 2024
The decreased VEGF expression leads to decreased angiogenesis and vascular permeability in liver metastases, ultimately reducing the occurrence of liver metastasis. Our findings highlight that overexpression of NAT1 significantly inhibits the PI3K/AKT/mTOR signaling pathway, thereby suppressing EMT, glycolytic ability, and VEGF expression in colorectal cancer cells, collectively preventing the development of liver metastasis.
- |||||||||| Journal: Single-cell genomics details the maturation block in BCP-ALL and identifies therapeutic vulnerabilities in DUX4-r cases. (Pubmed Central) - Jul 5, 2024
Given the multilineage priming of the DUX4-r blasts with aberrant expression of the myeloid marker CD371 (CLL-1), we generated chimeric antigen receptor T cells, which effectively eliminated DUX4-r ALL cells in vivo. These results provide a detailed characterization of BCP-ALL at the single-cell level and reveal therapeutic vulnerabilities in the DUX4-r subtype with implications for the understanding of ALL biology and new therapeutic strategies.
- |||||||||| Journal: Cannabidiol Alleviates Oral Mucositis by Inhibiting PI3K/Akt/NF-?B-Mediated Pyroptosis. (Pubmed Central) - Jul 5, 2024
In vitro experiments indicated that CBD enhanced HOK cell proliferation and migration and reduced apoptosis through inhibition of the PI3K/Akt/NF-?B signaling pathway and pyroptosis. Our findings suggest a novel mechanism for controlling OM, in which CBD suppresses the PI3K/Akt/NF-?B signaling pathway and pyroptosis, thereby mitigating OM symptoms.
- |||||||||| Review, Journal: Novel therapeutic strategies and drugs for idiopathic pulmonary fibrosis. (Pubmed Central) - Jul 4, 2024
Through a summary of current research progress, it is found that natural products possess multitarget effects, stable therapeutic efficacy, low side effects, and nondrug dependence. Furthermore, we discuss the significant prospects of natural product molecules in combating fibrosis by influencing the immune system, expecting that current analytical data will aid in the development of new drugs or the investigation of active ingredients in natural products for potential IPF treatments in the future.
- |||||||||| Herceptin (trastuzumab) / Roche, Perjeta (pertuzumab) / Roche
Preclinical, Review, Journal: Mechanisms of Acquired Resistance to HER2-Positive Breast Cancer Therapies Induced by HER3: A Comprehensive Review. (Pubmed Central) - Jul 1, 2024 The review also explores the resistance mechanisms associated with various drugs, including trastuzumab, lapatinib, and PI3K inhibitors, providing insights into the intricate molecular processes underlying resistance development. The review concludes by emphasizing the necessity for further clinical trials to assess the efficacy of HER3 inhibitors and the potential of developing safe and effective anti-HER3 treatments to improve treatment outcomes for patients with HER2-positive breast cancer.
- |||||||||| Journal: Potency and efficacy of pharmacological PIP4K2 inhibitors in acute lymphoblastic leukemia. (Pubmed Central) - Jul 1, 2024
In summary, our findings elucidate the differential expression of PIP4K2-related genes in ALL and underscore the potential role of PIP4K2A in disease pathogenesis. The therapeutic promise of THZ-P1-2 in ALL treatment, along with its distinct effects on cell death mechanisms and signaling pathways, enriches our understanding of PIP4K2's involvement in ALL development and offers targeted therapy prospects.
- |||||||||| Elaspol (sivelestat) / Ono Pharma
Journal, IO biomarker: Sivelestat improves acute lung injury by inhibiting PI3K/AKT/mTOR signaling pathway. (Pubmed Central) - Jun 27, 2024 REST positively regulates autophagy and negatively affects the Akt/mTOR signaling pathway in GC cells in a FABP6-dependent manner, providing valuable insights into regulatory networks involving FABP6 and REST. Sivelestat sodium has an interventional effect on ALI in sepsis by inhibiting the PI3K/AKT/mTOR signalling pathway.
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