- |||||||||| LY294002 / Eli Lilly, SB225002 / GSK
Journal: Chemokine receptor CXCR2 in primary sensory neurons of trigeminal ganglion mediates orofacial itch. (Pubmed Central) - Nov 13, 2023 Collectively, we report that CXCR2 in the primary sensory neurons of trigeminal ganglion contributes to orofacial itch through the PI3K/Akt signaling pathway. These observations highlight the potential of molecules involved in the regulation of CXCR2 as viable therapeutic targets for the treatment of itch.
- |||||||||| PTEN loss in glioma cell lines facilitates immune evasion by upregulating extracellular vesicle biogenesis and PD-L1 cargo (Exhibit Hall A/B) - Nov 11, 2023 - Abstract #SNO2023SNO_501;
Taken together, these findings shed new light on how the loss of a major tumor suppressor, PTEN, can alter EV biogenesis and function and contribute to an immunosuppressive extracellular milieu. Future studies will be directed toward exploring whether loss of PTEN function alters additional EV-associated immuno-modulatory proteins relevant to other immune cell populations, toward gaining a further understanding of how EVs shape the
- |||||||||| neflamapimod (VX-745) / CervoMed, PIK-75 / VetDC, SP600125 / BMS
A NOVEL DRUG TARGET: IL-36 SIGNALLING DRIVES INFLAMMATION AND POOR BACTERIAL CLEARANCE IN COPD (Windsor, 5th floor) - Nov 11, 2023 - Abstract #BTSWM2023BTS_WM_182; As IL36g is secreted in response to viral stimuli, the effects of IL36g described above could be important in pathogenesis of COPD exacerbations and secondary bacterial infection. IL36RN is reduced in COPD macrophages, which may be due to PI3K expression which is increased in COPD: Further work is needed to identify how this pathway regulates IL36RN to identify a potential drug target.
- |||||||||| Entresto (sacubitril/valsartan) / Novartis, ROVI Pharmaceuticals Laboratories
Preclinical, Journal: Combination of sacubitril/valsartan and blockade of the PI3K pathway enhanced kidney protection in a mouse model of cardiorenal syndrome. (Pubmed Central) - Nov 9, 2023 Adding PI3K inhibitor treatment to ARNI ameliorated kidney injury to levels comparable with those of ANS-VAL M while preserving the superior cardioprotective effect of ARNI. PI3K pathway activation has been identified as a key mechanism affecting remnant kidney injury under ARNI treatment in CRS pathology, and blockading the PI3K pathway with simultaneous ARNI treatment is a potential therapeutic strategy for treating CRS with overt albuminuria.
- |||||||||| Journal: Genetic silencing of AKT induces melanoma cell death via mTOR suppression. (Pubmed Central) - Nov 6, 2023
Furthermore, this single agent targeted therapy was well tolerated in vivo and was effective against MAPK inhibitor resistant patient-derived melanoma xenografts. These results suggest that inhibition of PI3K and mTOR with this novel dual inhibitor may represent a promising therapeutic strategy in this disease in both the first line and MAPK inhibitor resistant setting.
- |||||||||| Journal: Dauricine regulates prostate cancer progression by inhibiting PI3K/AKT-dependent M2 polarization of macrophages. (Pubmed Central) - Nov 6, 2023
Taken together, our data demonstrated that Dau suppressed M2 polarization of macrophages via downregulation of the PI3K/AKT signaling pathway, in turn, preventing proliferation, epithelial-mesenchymal transition, migration, and invasion of PCa cells. Thus, this study reveals a previously unrecognized function of Dau in inhibition of PCa progression via intervention in M2 polarization of macrophages.
- |||||||||| Orencia (abatacept) / BMS
Journal: Monogenic forms of common variable immunodeficiency and implications on target therapeutic approaches. (Pubmed Central) - Nov 6, 2023 Thus, this study reveals a previously unrecognized function of Dau in inhibition of PCa progression via intervention in M2 polarization of macrophages. Understanding the biological basis of CVID is important not only for enriching our knowledge of the human immune system, but also for setting the basis for potential targeted treatments in this disorder.
- |||||||||| fluoxetine / Generic mfg.
Fluoxetine exerts anti-inflammatory effects on human epidermal keratinocytes, and suppresses their endothelin release () - Nov 6, 2023 - Abstract #ISDS2023ISDS_327; Collectively, our findings demonstrate that fluoxetine exerts potent anti-inflammatory effects, and suppresses the release of the endogenous itch mediator endothelins in human keratinocytes, most likely via indirect inhibition of PI3K. Thus, clinical studies are encouraged to explore whether the currently reported beneficial effects translate in vivo following its topical administration in inflammatory and pruritic dermatoses.
- |||||||||| Enhertu (fam-trastuzumab deruxtecan-nxki) / Daiichi Sankyo, AstraZeneca
Clinical and genomic landscape of ERBB2 and ERBB3 mutated breast cancer (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_1852; We identify a notable enrichment of ERBB2/3-mut in lobular histology and metastatic tumors and tendency for co-alteration with CDH1 and multiple transcription factors reflecting the unique biology of ERBB2/3-mut breast cancers. Further analyses on an expanded cohort (n >6000 pts), including outcomes on HER2-directed antibody-drug conjugates (T-DXd) and targeted therapies such as PI3K inhibitors, will be presented at the 2023 SABCS Annual Meeting.
- |||||||||| letrozole / Generic mfg.
Ketogenic diet and letrozole to inhibit PI3K signaling in ER+ breast cancer (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_1060; For both groups, cell proliferation will be measured in a tumor biopsy obtained from the surgical specimen and compared with the pre-treatment diagnostic biopsy. Correlative studies will evaluate tumor markers of insulin/PI3K signaling before and after the intervention and between diet and control.
- |||||||||| SURVIVE study (Hall 2-3) - Nov 4, 2023 - Abstract #SABCS2023SABCS_654;
P=N/A The SURVIVE-study is a long-awaited trial in early breast cancer follow-up, based on promising liquid biopsy markers. If successful, the results will lead to a paradigm shift in current follow-up care of intermediate to high-risk early breast cancer survivors.
- |||||||||| LY294002 / Eli Lilly
Journal: The eNOS-induced leonurine's new role in improving the survival of random skin flap. (Pubmed Central) - Nov 3, 2023 And this protective function was inhibited by LY294002 (a broad-spectrum inhibitor of PI3K) and L-NAME (NG- nitro-L-arginine methyl ester, a non-selective NOS inhibitor)...By encouraging angiogenesis, preventing inflammation, minimizing oxidative stress, and lowering apoptosis, Leo can raise the survival rate of random skin flaps. The recommended concentration of Leo in this study was 30
- |||||||||| LY294002 / Eli Lilly, Ex-Rad (recilisib) / Onconova
Preclinical, Journal: Effects of the PI3K/Akt/HO-1 pathway on autophagy in a sepsis-induced acute lung injury mouse model. (Pubmed Central) - Nov 3, 2023 Preclinically validated combination therapies hold promise for NF2 patients and warrants further study in clinical trials. Furthermore, when PI3K inhibitors LY294002, PI3K activators Recilisib and hemin were administered before the surgery, Akt, p-Akt, HO-1, and LC3-II levels were measured 24
- |||||||||| pictilisib (GDC-0941) / Roche
Journal: A Novel Dual PI3K/mTOR Inhibitor, XIN-10, for the Treatment of Cancer. (Pubmed Central) - Nov 3, 2023 Meanwhile, through the results of protein blotting and PCR experiments, we concluded that XIN-10 can block the activation of the downstream pathway of mTOR by inhibiting the phosphorylation of AKT(S473) as well as having significant inhibitory effects on the gene exons of PI3K and mTOR. These results indicate that XIN-10 is a highly potent inhibitor with low toxicity and has a strong potential to be developed as a novel PI3K?/mTOR dual inhibitor candidate for the treatment of positive breast cancer.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute
Computational Approach Based on Independent Drug Action Identifies Clinically Relevant Combinations for Acute Myeloid Leukemia (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6482; After accounting for monotherapies that displayed pan-toxicity across healthy samples and primary AML samples (mean DSS > 95 th percentile), we found venetoclax as the top combination partner of the top 100 most effective predicted combinations (FPMTB, n = 33; Beat-AML, n = 35)...Our approach enables the major advantage of identifying effective combinations for the entire patient population as an alternative to personalized combinations. Further associations with genetic makeup and transcriptomics signature can be leveraged to identify suitable combinations.
- |||||||||| Venclexta (venetoclax) / Roche, AbbVie, Walter and Eliza Hall Institute
Clinical Outcomes in Patients Treated with Both Covalent Btkis and Venetoclax and the Significance of (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6100; Pts with double refractory disease had a significantly shorter PFS and OS compared to others. These data are particularly relevant to clinical practice as they encourage participation in clinical trials and inform the design of trials investigating novel agents in this space.
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