CYP2C8 (Cytochrome P450 Family 2 Subfamily C Member 8)

Results from gain and loss of functional experiments indicated that BARD1 functions as a tumour suppressor during paclitaxel treatment, and BARD1 down-regulation increased the IC50 of paclitaxel from 2.46 nM to 5.33 nM in SK-OV-3 cells and from 3.11 nM to 7.51 nM in CaoV-3 cells. We are the first to demonstrate that the down-regulation of BARD1 contributes to paclitaxel resistance via up-regulating CYP2C8 in patients with OC, which provides a potent target for clinical OC treatment.

This study highlights the critical role of macrophage-associated transcriptomic remodeling in liver disease progression. The machine learning-based predictive models offer a promising approach for early diagnosis and clinical decision-making in patients with cirrhosis.

The use of explainable artificial intelligence techniques further supports their integration into precision oncology. Future research should focus on multicenter validation, real-time EHR integration, and the development of neuroprotective strategies for high-risk patients.

Based on the indicators used (Ki, IC50, IC50 shift, and [I]/Ki ratios), propoxazepam is not expected to be a significant CYP2C8 inhibitor in vitro.

Integrating genetic markers into clinical practice can facilitate personalized treatment strategies, minimizing PIPN risk and enhancing therapeutic outcomes. Further studies are needed to validate these findings across diverse populations and uncover novel genetic determinants.

The risk assessment model formulated in our research stands as a formidable instrument for forecasting BLCA prognosis, while also providing insights into the disease's progression mechanisms and guiding clinical decision-making strategies.

CYP2J2 exhibited similar Michaelis (Km) and substrate inhibition (Ks) constants; however, CYP2C8 had a lower Ks value, indicating more potent substrate inhibition in CYP2C8 than that in CYP2J2. To determine the effects of a given drug on arachidonic acid 14,15-epoxidation during drug development, experiments should be recommended with arachidonic acid of <20 μM for CYP2J2 and <5.0 μM for CYP2C8.

The metabolic diversity and dual character of biological effects of CYPs underlie their implications in, preliminarily, hormone-sensitive cancers. Variations in CYP activities and CYP gene polymorphisms are implicated in the interindividual variability in cancer and drug susceptibility. The development of CYP inhibitors provides options for personalized anticancer therapy.

Furthermore, the hydroxyl group at the C7 position of PTX plays a catalytic role by facilitating the hydrogen abstraction and rebound steps. Our study also confirms a pronounced stability of the transition state in the high-spin sextet spin state, enabled by the enzyme's specific substrate positioning.

Furthermore, drug sensitivity analysis through the pRRophetic algorithm suggested potential targeted therapies, revealing drugs with differential sensitivity based on LMA scores and varied treatment responses related to the expression of core genes. This study not only highlights the crucial role of lipid metabolism and acetylation in osteosarcoma but also offers a foundation for personalized treatment strategies, marking a notable advancement in combating this severe form of adolescent cancer.

Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.

Combined, the presented analyses mapped the genetic and inferred functional variability of CYP2C8 with high ethnogeographic resolution. These results can serve as a valuable resource for CYP2C8 allele frequencies and distribution estimates of CYP2C8 phenotypes that could help identify populations at risk upon treatment with CYP2C8 substrates. The high variability between ethnic groups incentivizes high-resolution pharmacogenetic profiling to guide precision medicine and maximize its socioeconomic benefits, particularly for understudied populations with distinct genetic profiles.