OSI-930 / Astellas - LARVOL DELTA

Physiologically based pharmacokinetic modeling of aldehyde oxidase drug-drug interactions mediated by erlotinib. (PubMed, Drug Metab Dispos) - "Recently, we characterized the epidermal growth factor receptor inhibitor erlotinib as a clinical AO inhibitor and proposed, through mechanistic metabolism studies and static modeling, that AO inhibition was responsible for its observed DDI with the investigational drug OSI-930...Additional simulations were also conducted to investigate untested clinical DDI scenarios between erlotinib and other known AO substrates-O6-benzylguanine, zaleplon, ziprasidone, and zoniporide...Additionally, our erlotinib model also predicts clinically significant DDIs would occur when dosing erlotinib with high fm,AO AO substrates. These findings highlight the need to consider AO inhibition in DDI risk assessments and may help inform future drug development and regulatory strategies."

Journal • PK/PD data • EGFR • SLCO2B1

Comprehensive Analysis and Experimental Validation of TLL2 as a Potential New Prognostic Biomarker Associated with Immune Infiltration in Lung Adenocarcinoma. (PubMed, Recent Pat Anticancer Drug Discov) - "For patients with LUAD, TLL2 may serve as an immunotherapeutic target and a useful prognosis biomarker."

Biomarker • IO biomarker • Journal • Asthma • Immunology • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pulmonary Disease • Respiratory Diseases • Solid Tumor • Transplant Rejection

The Drug-Drug Interaction Between Erlotinib and OSI-930 is Mediated Through Aldehyde Oxidase Inhibition. (PubMed, Drug Metab Dispos) - "Significance Statement In this study, we delineate an AO metabolic pathway in the investigational drug OSI-930 for the first time and confirmed that it represented a major route of metabolism through reaction phenotyping in human hepatocytes. Our study provided compelling mechanistic and modelling evidence for the first instance of an AO-mediated clinical DDI stemming from the in vivo inhibition of the AO-mediated quinoline 2-oxidation pathway in OSI-930 by erlotinib."

Journal • EGFR

A combination of cuproptosis and lncRNAs predicts the prognosis and tumor immune microenvironment in cervical cancer. (PubMed, Discov Oncol) - "In conclusion, we constructed five cuprotosis-related lncRNA prognostic models, which may be new tumor therapeutic targets for the prevention and treatment of cervical cancer."

Journal • Tumor mutational burden • Cervical Cancer • Oncology • Solid Tumor • Targeted Protein Degradation • TMB

Vertical pathway inhibition of receptor tyrosine kinases and BAD with synergistic efficacy in triple negative breast cancer. (PubMed, NPJ Precis Oncol) - "Additionally, combinatorial oncology compound library screening demonstrated that NCK synergized with tyrosine kinase inhibitors (TKIs), specifically OSI-930 or Crizotinib in reducing cell viability and promoting apoptosis of TNBC cells. In patient-derived TNBC xenograft models, NCK prolonged survival times of host animals, and in combination with TKIs generated superior survival outcomes to single agent treatment. Hence, this study provides proof of concept to further develop rational and mechanistic based therapeutic strategies to ameliorate the outcome of TNBC."

Journal • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer

NR4A1 as a potential therapeutic target in colon adenocarcinoma: a computational analysis of immune infiltration and drug response. (PubMed, Front Genet) - " Our findings suggest that targeting NR4A1 with OSI-930 may be a promising therapeutic strategy for COAD patients with high levels of immune infiltration. However, further studies are needed to investigate the clinical efficacy of this approach."

Journal • Colon Cancer • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Cancer • Oncology • NR4A1

Inhibition of VEGF receptors induces pituitary apoplexy: An experimental study in mice. (PubMed, PLoS One) - "Here, we found that mice administered with OSI-930, an inhibitor of receptor tyrosine kinases including VEGF receptor 1 and 2, frequently exhibited hemorrhage in the pituitary gland...Our study demonstrates that anti-VEGF agents have a risk of pituitary apoplexy. Pituitary apoplexy should be kept in mind as an adverse effect of anti-VEGF therapy."

Journal • Preclinical • Endocrine Cancer • Hematological Disorders • Oncology • Pituitary Gland Carcinoma • CDH5 • PDGFRB

A Pan-Cancer Analysis Reveals CLEC5A as a Biomarker for Cancer Immunity and Prognosis. (PubMed, Front Immunol) - "The drug sensitivity analysis screens out potential therapeutic agents associated with CLEC5A expression, including FR-180204, Tivozanib, OSI-930, Linifanib, AC220, VNLG/124, Bexarotene, omacetaxine mepesuccinate, narciclasine, leptomycin B, PHA-793887, LRRK2-IN-1, and CR-1-31B. CLEC5A overexpresses in multiple cancers in contrast to normal tissues, and high CLEC5A expression predicts poor prognosis of patients and immune infiltration. CLEC5A is a potential prognostic biomarker of diverse cancers and a target for anti-tumor therapy."

Biomarker • Journal • Pan tumor • Immune Modulation • Immunology • Infectious Disease • Inflammation • Oncology • CAFs • MSI • TMB

Identification of a unique tumor cell subset employing myeloid transcriptional circuits to create an immunomodulatory microenvironment in glioblastoma. (PubMed, Oncoimmunology) - "Treatment of OSI-930 as a molecular agent targeting c-kit and VEGFR2 tyrosine kinases may compromise the immunomodulatory signature of C3 GBMs and synergize with chemo-radiation therapy. We further developed a simplified 11-gene set for defining C3 GBMs. Our work identified TC-6 subset as an immune-evading hub that creates an immunomodulatory signature of C3 GBMs, gaining insights into the heterogeneity of GBM immune microenvironment and holding promise for optimized anti-GBM immunotherapy."

Journal • Brain Cancer • Glioblastoma • Immune Modulation • Inflammation • Oncology • Solid Tumor • IRF1 • IRF2 • IRF7 • KDR • KIT • STAT1 • STAT2