CYP3A4 and CYP3A5: the crucial roles in clinical drug metabolism and the significant implications of genetic polymorphisms

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e18636 - e18636

Published: Dec. 5, 2024

CYP3A, a key member of the cytochrome P450 (CYP450) superfamily, is integral to drug metabolism, processing substantial portion medications. Their role in metabolism particularly prominent, as CYP3A4 and CYP3A5 metabolize approximately 30–50% known drugs. The genetic polymorphism CYP3A4/5 significant inter-individual variability enzymatic activity, which can result different pharmacokinetic profiles response same among individuals. These polymorphisms lead either increased toxicity or reduced therapeutic effects, requiring dosage adjustments based on profiles. Consequently, study activity gene variants great importance for formulation personalized treatment regimens. This article first reviews human body, including inhibitors inducers drug-drug interactions. In terms polymorphism, it discusses detection methods, kinetic characteristics, clinical guidelines CYP3A5. Finally, summarizes applications, therapy, management interactions, adjustment doses. review contributes understanding functions characteristics CYP3A4/5, allowing more effective outcomes through optimized therapy.

Language: Английский

---

DNA Repair Capacity and Clinicopathological Characteristics in Puerto Rican Hispanic/Latino Patients with Metastatic Castration-Resistant Prostate Cancer

Cancers, Journal Year: 2025, Volume and Issue: 17(2), P. 279 - 279

Published: Jan. 16, 2025

Background: Prostate cancer (PCa) accounts for 22% of the new cases diagnosed in Hispanic/Latino (H/L) men US. PCa has highest incidence (38.3%) and mortality (16.4%) among all types Puerto Rico. We previously showed that patients (n = 41) have a significant reduction 59% their levels DNA repair capacity (DRC) when compared to controls 14). This study aimed evaluate DRC through nucleotide excision (NER) pathway first time 16 Rican H/L with metastatic castration-resistant (mCRPCa) while establishing comparisons indolent aggressive disease. Methods: Blood samples clinicopathological data from 71) 25) were evaluated. stratified into mCRPCa 16), 31), 24). NER measured lymphocytes CometChip assay. The stratification by Gleason score (GS) was GS6 7), GS7 23), GS ≥ 8 20), 16). Results: Significant statistical differences found comparing values any other four patient groups. had lowest mean level groups studied. 6.65%, controls, this represented statistically 62% (p < 0.0001). Further analysis performed contributions age, anthropometric measurements, prostate-specific antigen (PSA) DRC. Kaplan–Meier curves revealed survival probability decreased approximately 50% 30 months. pilot uses blood-based phenotypic assay present report at global patients. Conclusions: evaluated mCRPCa. between three months, only 20% cohort alive 50 confirming lethality population. represents using

Language: Английский

---

Current Evidence on Cabazitaxel for Prostate Cancer Therapy: A Narrative Review

International Journal of Urology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 25, 2025

The incidence of prostate cancer (PC) has recently increased in Japan. Androgen deprivation therapy (ADT) been a key treatment patients with castration-sensitive PC (CSPC); however, resistance typically emerges through multiple mechanisms, leading to metastatic castration-resistant (mCRPC). Taxane-based (i.e., docetaxel, cabazitaxel) standard care mCRPC. New evidence supporting the addition androgen receptor signaling inhibitors (ARSIs, e.g., enzalutamide, abiraterone) docetaxel and ADT for CSPC (mCSPC) raises questions about role taxane-based therapies their optimal sequencing, as well how identify who may benefit from therapy. Here we review on therapy, including cabazitaxel, PC, focus clinical real-world Cabazitaxel proven effective mCRPC have history ARSI use, it is preferable second alternative ARSI, indicated CARD study. safety profile cabazitaxel (particularly, neutropenia) can be managed prophylactic use granulocyte colony-stimulating factor, lower dosage possibly variation interval. However, certain dose intensity required because neutropenia identified potential prognostic indicator effectiveness. In era mCSPC, sequencing limited. A better understanding biology collection data essential improved safety-benefit outcomes.

Language: Английский

---

Comparative therapeutic efficacy and safety of first-line and second-line therapies for metastatic castration-resistant prostate cancer: a systematic review and network meta-analysis

EClinicalMedicine, Journal Year: 2025, Volume and Issue: 81, P. 103129 - 103129

Published: Feb. 28, 2025

Language: Английский

---

N6-methyladenosine-modified circQKI inhibits prostate cancer docetaxel-sensitivity via miR-188-3p/Beclin-1 pathway

Life Sciences, Journal Year: 2025, Volume and Issue: 372, P. 123646 - 123646

Published: April 17, 2025

Language: Английский

---

Management Decisions for Metastatic Castration-resistant Prostate Cancer in 2024

European Urology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

---