UGT2B17 (UDP Glucuronosyltransferase Family 2 Member B17)

This article systematically explores the association between the UGT2B subfamily and hormone-dependent prostate cancer, covering various aspects such as gene function, regulatory mechanisms, disease progression, and diagnosis. It elucidates the different roles of UGT2B genes and reveals their significant potential in being developed into biomarkers and therapeutic targets, paving the way for improvements in precision medicine for prostate cancer.

It was stated that the AHR, EPHX1, GSTP1, and SLC25A32 did not correlate in healthy intestinal tissue whereas AHCY, ALDH1A1, NNMT, GSTM4, UGT2B17, and SLCO1B3 did not correlate in CRC. The disturbed transcriptional activity of genes related to the biotransformation process at all stages of CRC suggests that this may be the cause of its occurrence; the genes ought to be taken into account in preventive strategies and the treatment of patients.

Targeting the newly identified UGT2B17 functions using a combination of inhibitors reduces tumor growth in therapy-resistant tumor models, highlighting a promising therapeutic strategy. Collectively, these findings reveal a mechanism by which prostate tumors exploit UGT2B17 to evade therapy and highlight its potential as a therapeutic target in advanced prostate cancer.

Additional studies evaluated the impact of strong CYP3A4 perpetrators and imatinib on a single 40 mg dose of asciminib. This PBPK model was applied in lieu of clinical pharmacology studies to support the new drug application of Scemblix® and to bridge data from 40 mg BID to the 80 mg QD and 200 mg BID dose regimens. The PBPK predictions informed the drug product label and are estimated to have replaced at least 10 clinical studies.

UGT2B17 expression influences hormone levels and identifies a subset of patients at an increased risk of progression to an incurable disease stage. Findings support the notion that enhanced UGT2B17, through increased androgen inactivation, creates a low-androgen tumor environment that drives tumor progression to a more aggressive phenotype.

The UGT2B17 genotype was found to contribute to substantial interindividual variability in the metabolism of EXE, however, GSTA1 genotype was also significantly associated with altered EXE metabolism. Given their high polymorphic allele frequency, genotypes of UGT2B17 and GSTA1 potentially play important roles in interindividual variability in patient response including EXE efficacy and toxicity.

Notably, this TIMP1+HBsAg-hALBlow phenotype was also observed in liver biopsies from chronic HBV patients, underscoring its clinical relevance. Our findings highlight HBV-driven metabolic adaptation and identify TIMP1 as a potential mediator of fibrosis in uninfected hepatocytes, offering novel insights into HBV pathogenesis and therapeutic targeting.

Our simulations predict that belzutifan decreases the exposure of combination therapies metabolized via CYP3A, with the severity of interaction dependent on CYP2C19 and UGT2B17 phenotypes.

Furthermore, novel pathogenic variants of AKR1D1, LIPC, and SERPINE1, associated with congenital bile acid synthesis defects, abnormal circulating lipid concentrations, and plasminogen activator inhibitor type 1 deficiency conditions, were identified. Conclusively, this integrative multiomics study highlights the novel pathogenic variants of AKR1D1, LIPC, and SERPINE1 in metabolic, immune, and lipid pathways that are highly expressed among hepatocytes in obese patients while possibly carrying pathogenic mutations that may be associated with NAFLD, emphasizing their potential as novel targets for therapeutic strategies and biomarker development in early diagnosis and treatment before the onset of cirrhosis or hepatocellular carcinoma.

Our researchers utilized a gene model to analyze the immune inflammation and prognosis of patients with non-small-cell lung cancer (NSCLC). The discovery of new ICD-related genes could lead to the development of new targeted treatments for this condition.

Other proteins of interest which could be quantified in colonic samples were the drug transporters P-gp, MRP3, MRP4, OATP2B1, MCT1 and enzymes CYP4F2, CYP2J2 and UGT1A1. The insights from this study enhance our understanding of the extent to which drug disposition in tumor tissue of colorectal cancer patients could be impacted by drug transporters and drug-metabolizing enzymes and may facilitate a more accurate prediction of local drug concentrations.

P1, N=30, Recruiting, Washington State University | Trial completion date: Aug 2024 --> Aug 2026 | Trial primary completion date: Aug 2024 --> Dec 2025