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27d
IGF1R inhibition and PD-1 blockade improve anti-tumor immune response in epithelial ovarian cancer. (PubMed, Front Oncol)
Additionally, anti-PD-1/IGF1R treatment increased DC by 34% compared with AEW-541 and 40% with anti-PD-1...RNA-seq data analysis indicated that anti-PD-1/IGF1R led to a more potent immune response, as reflected by altered gene expression levels related to anti-tumor immune response, compared with either treatment alone. These findings provide novel evidence that IGF1R axis inhibition combined with PD-1 blockade may be an effective therapeutic strategy for selected EOC patient populations.
Journal • PD(L)-1 Biomarker • IO biomarker
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CD8 (cluster of differentiation 8) • IGF1 (Insulin-like growth factor 1)
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NVP-AEW541
2ms
Signaling effect, combinations, and clinical applications of triciribine. (PubMed, J Chemother)
Triciribine (TCN) is a tricyclic nucleoside. Although a single dose of TCN demonstrated limited activity in solid tumors at the clinical level, combinations of TCN with various agents, such as specific inhibitors, tyrosine kinase inhibitor dasatinib, ErbB inhibitor tipifarnib, IGF1-R inhibitor NVP-AEW541, mTORC1 inhibitor RAD-001, TNF-related apoptosis-inducing ligand, PPARγ agonist, 1,25(OH)2D3, gemcitabine, and paclitaxel, have been reported to be efficient against various malignancies such as pancreatic, breast, prostate cancer, insulinoma, gut neuroendocrine tumor, and hepatocellular carcinoma at the preclinical level. Other than malignancies, through Akt inhibition activity, TCN has also been demonstrated potential for treating lung injuries, including those encountered in COVID-19 infections.
Review • Journal
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IGF1 (Insulin-like growth factor 1)
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dasatinib • gemcitabine • paclitaxel • everolimus • Zarnestra (tipifarnib) • NVP-AEW541 • triciribine phosphate (PTX-200)
9ms
IGF-1R mediates crosstalk between nasopharyngeal carcinoma cells and osteoclasts and promotes tumor bone metastasis. (PubMed, J Exp Clin Cancer Res)
The intricate interplay among IGF-1R, IGF-1, and GM-CSF highlights potential therapeutic targets for precise control of NPC bone metastasis, providing valuable insights for developing targeted interventions.
Journal
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CSF2 (Colony stimulating factor 2)
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IGF1 elevation
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sirolimus • NVP-AEW541
over3years
IGF2 Mediates Resistance to Isoform-Selective-Inhibitors of the PI3K in HPV Positive Head and Neck Cancer. (PubMed, Cancers (Basel))
Here, we delineate the molecular mechanisms of the acquisition of resistance to two isoform-selective inhibitors of PI3K (isiPI3K), alpelisib (BYL719) and taselisib (GDC0032), in HNC cell lines...Knocking-down IGF2 with siRNA, or blocking IGF1R with AEW541, resulted in superior anti-tumor activity of isiPI3K in vitro and ex vivo. In vivo, the combination of isiPI3K and IGF1R inhibitor induced stable disease in mice bearing either tumors generated by the HNC UM-SCC47 cell line or HPV+ patient-derived xenografts. These findings indicate that IGF2 and the IGF2/IGF1R pathway may constitute new targets for combination therapies to enhance the efficacy of PI3K inhibitors for the treatment of HNC.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2)
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Piqray (alpelisib) • taselisib (GDC-0032) • NVP-AEW541
over4years
[VIRTUAL] Combination of insulin-like growth factor-1 receptor/insulin receptor (IGF1R/IR) antagonist with anti-PD-L1 antibody blocks triple-negative breast cancer (TNBC) progression (AACR-II 2020)
Combination treatment of BMS-754807 (IGF1R/IR) with NVP-AEW541 (IGF1R inhibitor) reduced proliferation of human MDA-MB-231, BT549, HCC1937 and murine 4T1 TNBC cells in vitro (P<0.001). Use of immunotherapy is a promising management option for a subset of TNBC patients, and combination treatments using IGF1R antagonists with immune checkpoint inhibitor may constitute a new treatment strategy to combat this deadly disease. &lsqb;Funding by NCI U54 CA1433930; California Breast Cancer Research Program; UCLA Jonsson
Late-breaking abstract • PD(L)-1 Biomarker • IO biomarker
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IGF1R (Insulin-like growth factor 1 receptor) • IGF1 (Insulin-like growth factor 1) • IGF2 (Insulin-like growth factor 2) • IR (Insulin receptor)
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MSLN positive
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BMS-754807 • NVP-AEW541
over4years
IGF-1 alleviates serum IgG-induced neuronal cytolysis through PI3K signaling in children with opsoclonus-myoclonus syndrome and neuroblastoma. (PubMed, Pediatr Res)
IGF-1/PI3K signaling alleviates the cytolysis of cultured neurons induced by serum IgG from children with OMS and NB, which may be innovation therapy targets.
Clinical • Journal
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IGF1 (Insulin-like growth factor 1)
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LY294002 • NVP-AEW541