J Clin Pharmacol. 2025 Jun 11. doi: 10.1002/jcph.70058. Online ahead of print.

ABSTRACT

Given the significant impacts of interindividual genetic variability on drug safety and pharmacokinetics, integrating pharmacogenetic (PGx) considerations into pharmacokinetic (PK) bioequivalence (BE) study design can improve subject safety and data robustness in generic drug development. While PGx information has been often utilized in new drug development, its use in generic drug development has not been fully considered. To understand the current landscape of its utility in generic drug development, product-specific guidances (PSGs) from the US Food and Drug Administration (FDA) containing PGx information were reviewed, along with study protocols submitted by generic drug applicants under abbreviated new drug applications (ANDAs) or controlled correspondences for the identified reference listed drugs (RLDs). Fifteen PSGs (15 RLDs) recommended PGx information as a consideration factor for subject population selection, particularly for drugs associated with inherited enzyme deficiencies or cytochrome P450 polymorphism. The PGx-based considerations in these PSGs aimed to prevent serious adverse events (60%), optimize PK BE study design (7%), or address both factors (33%). Among the 15 RLDs, 5 had submitted ANDAs or correspondences with PK BE study protocols after their respective PSGs were published. Most of these submissions aligned with the PSG recommendations, incorporating PGx-related exclusion criteria. These findings suggest that while the number of submissions is low, generic drug developers are increasingly integrating PGx considerations in PK BE studies, recognizing its potential to enhance safety and efficiency in generic drug development. Continuing efforts from both regulators and industry are critical to expand its application to other drug candidates.

PMID:40501016 | DOI:10.1002/jcph.70058

Discov Oncol. 2025 Jun 11;16(1):1056. doi: 10.1007/s12672-025-02905-5.

ABSTRACT

BACKGROUND: Metastasis, the spread of cancer cells from the primary tumor to distant organs, is the leading cause of mortality in cancer patients. This process often exhibits a preference for specific organs, a phenomenon known as tumor organotropism. This study focuses on the organotropism of breast cancer and analyzes its genomic alterations following metastasis to four organs (bone, brain, liver, and lung). The research aims to explore the intrinsic characteristics of primary breast cancer and the interactions between tumor cells and the tumor microenvironment (TME) within these target organs. Building upon this foundation, we developed a deep learning model to identify organ-specific metastatic genes, providing insights into the molecular mechanisms of metastasis.

METHODS: To investigate the mechanisms of organ-specific metastasis in breast cancer, we employed an integrative approach combining single-cell RNA sequencing, bulk RNA sequencing, ChIP-seq data, and deep learning techniques. Single-cell analysis provided detailed insights into cellular heterogeneity and microenvironment interactions at metastatic sites. Bulk RNA sequencing enabled the identification of gene expression patterns associated with metastatic propensity. A deep neural network (DNN) model was developed to analyze these complex datasets and identify key predictors of organ-specific metastasis.

RESULTS: Our integrative analysis revealed distinct gene expression profiles and cellular compositions in metastatic lesions across different organs. We have identified that, regardless of the target organ, breast cancer metastasis critically depends on specific biological signaling pathways, including the MAPK signaling pathway, metabolic pathways, the PI3K-Akt signaling pathway, and the positive regulation of cell adhesion. Single-cell sequencing highlighted unique interactions between tumor cells and the microenvironment, which varied significantly depending on the metastatic site. Fibroblasts play a critical role in facilitating the colonization of breast cancer cells in metastatic organs. The deep learning models effectively identified key molecular signatures and pathways associated with organ-specific metastasis, providing insights into the metastatic process.

CONCLUSION: The study underscores the importance of the tumor microenvironment in influencing breast cancer metastasis to distant organs. We also established a comprehensive framework for understanding the mechanisms driving organotropism metastasis in breast cancer. Additionally, we identified key genes and signaling pathways associated with organ-specific metastasis, providing insights that may inform future studies on risk assessment and potential therapeutic targets for metastatic breast cancer.

PMID:40500539 | DOI:10.1007/s12672-025-02905-5

ESMO Open. 2025 Jun 10;10(6):105119. doi: 10.1016/j.esmoop.2025.105119. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-drug interactions (DDIs) are a critical challenge in managing cancer patients receiving polytherapy, often due to comorbid conditions. DDIs can arise through pharmacokinetic mechanisms, affecting drug absorption, distribution, metabolism, or excretion, or through pharmacodynamic interactions, altering drug target binding or leading to overlapping toxicities. These interactions can compromise treatment efficacy, exacerbate adverse events, and increase patient morbidity and mortality.

METHODS: Effective DDI management requires a multidisciplinary approach that integrates oncologists and pharmacologists. Key factors influencing DDIs include the pharmacological properties of drugs, patient-specific clinical and genetic characteristics, and the timing of therapy exposure. Identifying and mitigating DDIs also relies on patients' adherence to treatment and their early reporting of adverse events.

RESULTS: This article proposes a structured framework for DDI assessment in oncology, emphasizing actionable strategies tailored to the complexities of cancer care. The framework incorporates the evaluation of pharmacokinetic and pharmacodynamic interactions, identification of high-risk drug combinations, and the use of therapeutic drug monitoring (TDM) and pharmacogenetics to individualize treatment. Specific recommendations for managing QTc-prolonging interactions, CYP3A4-mediated metabolism, and P-glycoprotein (P-gp)-related transport issues are highlighted.

CONCLUSIONS: By fostering collaboration among health care professionals and leveraging advanced tools, the proposed approach aims to optimize therapeutic outcomes while minimizing DDI risks. The manuscript underscores the importance of tailored strategies in oncology, advocating for the integration of pharmacological insights into clinical practice to enhance patient safety and treatment efficacy.

PMID:40499461 | DOI:10.1016/j.esmoop.2025.105119

Mol Neurobiol. 2025 Jun 11. doi: 10.1007/s12035-025-05133-8. Online ahead of print.

ABSTRACT

The brain requires a large amount of energy, primarily obtained through glucose metabolism, which appears to be disrupted in various neuropsychiatric disorders. The etiology of neuropsychiatric disorders is complex and involves genetic factors that are slowly being identified. To investigate whether glucose metabolism-related genes are associated with major psychiatric disorders, we conducted secondary analyses using genome-wide association study (GWAS) summary statistics for major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ). Based on predefined glucose metabolism pathway genes, we conducted a multi-layer integrative analysis using gene-level approaches including multi-marker analysis of genomic annotation (MAGMA), transcriptome-wide association studies (TWAS) with joint-tissue imputation (JTI), and summary-based Mendelian randomization (SMR). We further explored gene expression patterns across tissues, druggability, and applied gene network analysis to evaluate the interactions. MAGMA identified 1 significant gene for MDD, 19 for BD, and 32 for SCZ, with gene RBKS shared across all three disorders. TWAS-JTI detected 17 and 35 transcriptome-wide significant genes for BD and SCZ, respectively, while SMR prioritized 2 and 9 putatively causal genes. For MDD, no convergent evidence emerged from TWAS-JTI or SMR analyses. Integrated analysis highlighted NDUFS2, NDUFS7, and NDUFC2 in the oxidative phosphorylation pathway as potential therapeutic targets. Finally, gene network analysis highlighted enrichment in mitochondrial respiratory chain complex I biogenesis, NADH dehydrogenase complex assembly, and ATP synthesis. Our results reinforce the role of energy metabolic disturbance in psychiatric disorders, particularly in BD and SCZ. These findings open avenues for targeted therapeutic interventions, warranting further validation across populations.

PMID:40498271 | DOI:10.1007/s12035-025-05133-8

Per Med. 2025 Jun 11:1-11. doi: 10.1080/17410541.2025.2515003. Online ahead of print.

ABSTRACT

AIMS: This study explored employees' understanding of, and psychosocial responses to, workplace genetic testing (wGT) results.

MATERIALS & METHODS: Employees of a US healthcare system who underwent wGT (hereditary cancer/heart disease risk, pharmacogenomics) and received results were surveyed. We ascertained pretest education engagement, test understanding, and psychosocial responses. Regression analyses identified predictors of scores on a modified Feelings About genomiC Test Results questionnaire (positive feelings, negative emotions, and uncertainty after wGT).

RESULTS: N = 418 employees (mean age = 44 years; 88.3% female; 80.6% white) completed the survey. Mean scores (out of 12; higher scores indicate a greater extent of each feeling) were 5.2 (SD = 2.9) for positive feelings, 1.2 (SD = 2.2) for negative emotions, and 2.0 (SD = 2.5) for uncertainty. Identifying as non-Hispanic African American/Black and receiving increased risk (cancer/heart disease) wGT results were associated with lower positive feelings and higher negative emotions and uncertainty scores (all p < 0.05). Open-ended responses indicated difficulty interpreting, recalling, and utilizing results.

CONCLUSIONS: wGT was associated with low levels of measured psychosocial harm among participants. However, results suggested a greater likelihood of negative psychosocial responses among those with increased risk of cancer/heart disease and non-Hispanic African American/Black employees. Future studies should explore strategies to ensure all employees undergoing wGT have educational and psychosocial support.

PMID:40497788 | DOI:10.1080/17410541.2025.2515003

Case Rep Psychiatry. 2025 Jun 2;2025:9811985. doi: 10.1155/crps/9811985. eCollection 2025.

ABSTRACT

Objective: Risk for mood and behavioral activation (MBA) due to selective serotonin reuptake inhibitors (SSRIs) is multiply determined in persons with Prader-Willi syndrome (PWS) due to underlying epigenetic and pharmacogenomic factors that affect medication response. Further, age and molecular subtype of PWS are predisposing factors, as there is a >60% risk for bipolar disorder onset prior to age 30 among those with maternal uniparental disomy (mUPD). This article presents two cases of MBA due to sertraline prescribed to treat anxiety in these adults with PWS (mUPD). Methods: Literature review, clinical experience, and data from group home behavior logs inform this case report. The assent of the patients and the consent of their parents (legal guardians) were obtained for this publication. Results: In these two cases, the gradual onset of MBA occurred over 1 year as the dose of sertraline was increased causing irritability, sleep disturbance, increased intensity of hyperphagia, and other phenotypic behaviors. These clinical signs were attributed to the stress of COVID-19 shutdown that resulted in loss of community activities for work, socialization, leisure, and exercise. But after sertraline was discontinued, activation resolved. Mood-stabilizing medication was required for a return to baseline, as sertraline may have unmasked or exacerbated an underlying bipolar diathesis. Conclusion: Sertraline and other SSRI medications can cause MBA in patients with PWS at typical starting doses, although risk for adverse effects increases with higher doses. Age is a contributing factor. Knowing the genetic subtype of PWS is essential for making clinical decisions about pharmacotherapy, and results of pharmacogenomic testing may inform the selection of medication, dose, and schedule of administration.

PMID:40496034 | PMC:PMC12149475 | DOI:10.1155/crps/9811985

Stroke. 2025 Jun 11. doi: 10.1161/STROKEAHA.124.049365. Online ahead of print.

ABSTRACT

BACKGROUND: A stroke's functional outcome presents vast variability among patients, which is influenced by age, sex, characteristics of the lesion, and genetic factors. However, there is little knowledge about stroke recovery genetics. Recently, some GWAS (Genome-Wide Association Studies) have highlighted the involvement of common or low-frequency variants near or within PATJ, PPP1R21, PTCH1, NTN4, and TEK genes, whereas the role of rare variants is still unclear. This study aims to identify the genetic contributions to differences in stroke outcomes by analyzing the effect of rare variants.

METHODS: We performed a pilot study analyzing 90 exomes of extreme good and bad recovery (modified Rankin Scale score at 3 months, 0-1 versus 4-5) to select target genes involved in stroke recovery. To expand this study, 702 additional samples were sequenced by targeted next-generation sequencing capturing loci selected from the pilot study, GWASs, and literature input. Here, we performed continuous (modified Rankin Scale score, 0-6) and dichotomous (modified Rankin Scale score, 0-1 versus 3-6) analyses, yielding 1 candidate gene. All samples were selected by a retrospective cohort study from incidental stroke cases collected at Spanish Hospitals between 2000 and 2018. The identified VNN2 variants were assessed for protein structure and stability analysis, and an analysis of their effect on basal inflammation levels was performed using UK Biobank data.

RESULTS: Our work identified rare coding variants in VNN2 associated with patients with better stroke recovery (∆ deviance information criterion >10, equivalent to P<0.001). Six rare variants were predicted to significantly affect protein stability (∆∆G >1.6 kcal/mol); meanwhile, another variant, located in the active site, could affect the electrostatic surface.

CONCLUSIONS: We propose that VNN2 might play a role in stroke outcomes by modulating poststroke inflammation. A potentially affected function would be neutrophil cell adhesion and migration.

PMID:40495801 | DOI:10.1161/STROKEAHA.124.049365

J Am Assoc Nurse Pract. 2025 Jun 10. doi: 10.1097/JXX.0000000000001140. Online ahead of print.

ABSTRACT

Pharmacogenetic testing is a rapidly evolving field that aims to improve the efficacy and safety of drugs by finding genetic links influencing how drugs are processed, their effectiveness, and toxicity. Due to the high incidence of adverse drug reactions (ADRs) associated with certain medications and the heterogeneity of drug responses among patients, pharmacogenetic testing has gained significant attention. Research has shown that many clinicians, including nurse practitioners (NPs), have limited knowledge and experience with pharmacogenomics and pharmacogenetic testing, highlighting the need for enhanced education in this area. Using pharmacogenetic information, NP can tailor medication regimens to personalize treatments to individual genetic profiles to improve results and reduce ADRs. This paper will apply the Genotype Selection Interface for pharmacogenetic testing and discuss its clinical application, including challenges, limitations, and future directions.

PMID:40493688 | DOI:10.1097/JXX.0000000000001140

Front Mol Biosci. 2025 May 26;12:1615533. doi: 10.3389/fmolb.2025.1615533. eCollection 2025.

ABSTRACT

BACKGROUND: Colorectal cancer (CRC) ranks among the most prevalent malignancies of the gastrointestinal tract and remains a leading cause of cancer-related mortality worldwide. Although telomere biology has been increasingly implicated in immune modulation and tumor progression, its clinical significance in CRC remains poorly understood.

METHODS: We developed a telomere score, termed TELscore, by integrating transcriptomic and intratumoral microbiome profiles from publicly available colorectal cancer (CRC) cohorts. To comprehensively characterize TELscore subgroups, we performed pathway enrichment analysis, tumor immune microenvironment (TIME) profiling, and microbiome niche assessment. Whole-slide histopathological images (WSIs) and immunohistochemical (IHC) staining were utilized to visualize immune features, including tertiary lymphoid structures (TLSs), across subgroups. Patients were stratified into high and low TELscore categories, and the predictive robustness was validated across multiple independent training and validation cohorts. Chemotherapeutic drug sensitivity was evaluated using pharmacogenomic data from the Genomics of Drug Sensitivity in Cancer (GDSC) database. Furthermore, the predictive capacity of TELscore for immunotherapy response was independently assessed in an external cohort. Finally, single-cell RNA sequencing (scRNA-seq) analysis was conducted to further dissect the cellular landscape and immunological heterogeneity within the TME.

RESULTS: TELscore stratified patients into two biologically and clinically distinct subgroups. The high TELscore group, which exhibited significantly shorter DFS, showed marked enrichment of tumorigenic pathways such as EMT, along with a distinctly immunosuppressive TME. This was reflected by elevated ESTIMATE/TIDE scores and corroborated by CIBERSORT, which revealed increased infiltration of M0 macrophages and upregulation of immunosuppressive signatures. In contrast, the low TELscore group was enriched for cell cycle related pathways, including E2F targets and the G2/M checkpoint, and demonstrated higher infiltration of pro-inflammatory M1 macrophages. 16S rRNA sequencing further revealed a divergent intratumoral microbiome between subgroups, the high TELscore group harbored significantly greater relative abundance of Selenomonas and Lachnoclostridium, two pathogenic genera previously associated with colorectal tumorigenesis. Complementary histopathological assessment via WSI demonstrated a marked absence of intraTLSs in high TELscore tumors. From a therapeutic standpoint, high TELscore tumors exhibited reduced sensitivity to standard chemotherapeutic agents-including Fluorouracil, Irinotecan, Oxaliplatin, and Docetaxel-as reflected by elevated IC50 values. Conversely, these tumors demonstrated increased susceptibility to MAPK pathway inhibitors, such as Selumetinib and Trametinib. Notably, TELscore also served as a robust predictor of immunotherapy response, which was validated in the IMvigor210 cohort. Finally, scRNA analysis highlighted profound cellular and functional divergence between TELscore subgroups. We identified intensified intercellular communication between inflammatory macrophages and fibroblasts, reinforcing the presence of an immunosuppressive niche.

CONCLUSION: TELscore is a robust stratification tool that captures the interplay between tumor biology, immune characteristics, and microbial ecology in colorectal cancer. By identifying clinically relevant subtypes with distinct therapeutic vulnerabilities, TELscore offers a powerful framework to advance personalized treatment and precision oncology.

PMID:40492114 | PMC:PMC12146184 | DOI:10.3389/fmolb.2025.1615533

Pharmacol Rep. 2025 Jun 9. doi: 10.1007/s43440-025-00746-1. Online ahead of print.

ABSTRACT

BACKGROUND: Statin usage has increased significantly in India due to the very high incidence of dyslipidemia, however, approximately 18% of the population is at risk for statin-induced myopathy. Hence, we conducted a population-level screening for pharmacogenetic determinants of statin therapy, particularly Solute Carrier Organic Anion Transporter Family Member 1B1 (SLCO1B1) and ATP-binding cassette sub-family G member 2 (ABCG2).

MATERIALS AND METHODS: Whole exome sequencing was performed in 2180 subjects, and the variant data were segregated further into diplotypes and phenotypes.

RESULTS: SLCO1B1 normal function was observed in 81% of subjects (diplotypes: 1/*1, *1/*14, *1/*20, *1/*37, and *37/*37). Increased SLCO1B1 function was observed in 8% of the population (diplotypes: *14/*14 and *20/*20). Decreased function of SLCO1B1 (*1/*15) was observed in 5% of the population. Poor function of SLCO1B1 was observed in 6% of the population (diplotypes: *5/*5 and *15/*15). About 81.46% of subjects displayed normal ABCG2 function, while 17.34% had decreased and 1.19% had poor function. Combined SLCO1B1/ABCG2 functional defects were observed in 7.4% of subjects. Two rare SLCO1B1 variants in SLCO1B1 i.e., rs201722521 and rs71581988, were reported to affect the binding affinity of certain statins. The SLCO1B1 C-C-C-A-A-A haplotype was associated with a 2.22-fold risk for hyperbilirubinemia (95% CI: 1.13-4.36, p = 0.02). Rosuvastatin's daily dose of up to 10 mg is well tolerated across the different SLCO1B1 functionality groups.

CONCLUSIONS: This study demonstrates that 11% of our population exhibit decreased or poor function of SLCO1B1 and 7.4% exhibit decreased or poor function of both SLCO1B1 and ABCG2, necessitating adjustments in daily statin doses to minimize the risk for statin-induced myopathy.

PMID:40489054 | DOI:10.1007/s43440-025-00746-1

Brain. 2025 Jun 9:awaf216. doi: 10.1093/brain/awaf216. Online ahead of print.

NO ABSTRACT

PMID:40488316 | DOI:10.1093/brain/awaf216

Am J Health Syst Pharm. 2025 Jun 9:zxaf141. doi: 10.1093/ajhp/zxaf141. Online ahead of print.

ABSTRACT

PURPOSE: Many healthcare professionals received little to no practical training on pharmacogenomics (PGx) during their degree programs. Due to a rapid influx of PGx into clinical practice, healthcare professionals face a need for education and support.

SUMMARY: We established a PGx Extension for Community Healthcare Outcome (ECHO) program, a telementoring and education model whereby healthcare professionals learn and acquire clinical skills through real-world case presentations. The goal was to provide clinical education, foster a community of practice, and promote health equity in PGx utilization by providing convenient virtual access to PGx expertise. Here we report on the first 2 years of the program and the delivery of 29 case sessions. Most learners (42%) are pharmacists, and participation has grown dramatically. At the time of enrollment, 57.6% of learners had previously received some form of PGx education prior to attending a session. Of these, only 17.6% felt very confident in their knowledge, 43.4% felt somewhat confident, and 24.7% were not confident in their knowledge. Participants were surveyed after each session through email. Of the attendee respondents, 94% agreed or strongly agreed that the sessions increased their knowledge, 88% reported increased skill in managing medications with PGx results, and 89% felt the education would improve their performance as health professionals. Notably, 54.9% of respondents indicated they would make changes to their practice primarily by using PGx to select a new medication and change a medication.

CONCLUSION: The PGx ECHO model is an effective tool to bring together experts and learners for education and mentoring.

PMID:40488313 | DOI:10.1093/ajhp/zxaf141

Acta Pharm Sin B. 2025 May;15(5):2511-2528. doi: 10.1016/j.apsb.2025.02.008. Epub 2025 Feb 11.

ABSTRACT

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

PMID:40487637 | PMC:PMC12145038 | DOI:10.1016/j.apsb.2025.02.008

Front Pharmacol. 2025 May 23;16:1584658. doi: 10.3389/fphar.2025.1584658. eCollection 2025.

ABSTRACT

INTRODUCTION: Pharmacogenomics investigates the impact of genetic variation on drug metabolism, enabling personalized medicine through optimized drug selection and dosing. This study examines the effect of the dynamic star allele nomenclature system on diplotypes and therapeutic recommendations using the GeT-RM dataset while also presenting a revised version to address outdated diplotypes.

MATERIALS AND METHODS: PharmVar data up to version 6.2 were downloaded to analyze the evolution of the star allele nomenclature system. FASTQ files from 70 samples of the GeT-RM project were downloaded and aligned to GRCh38, followed by star allele calling using Aldy, PyPGx, and StellarPGx. Diplotypes of the samples were updated based on predefined criteria. Phenotype predictions and therapeutic recommendations were inferred using the PyPGx core API, with CPIC guidelines applied for statin-phenotype combinations.

RESULTS: We reevaluated 1400 diplotypes across 20 pharmacogenes in 70 samples from the GeT-RM dataset using three star allele callers: Aldy, PyPGx, and StellarPGx. Our analysis revealed inconsistencies in 15 of 20 pharmacogenes, with 272 (19.4%) diplotypes being outdated. SLCO1B1 showed the highest number of discrepant calls, impacting statin dosing recommendations for NA19226.

DISCUSSION: Our findings demonstrate that outdated allele definitions can alter therapeutic recommendations, emphasizing the need for standardized approaches including mandatory PharmVar version disclosure, implementation of cross-tool validations, and incorporation of confidence metrics for star allele calling tools to ensure reliable pharmacogenomic testing.

PMID:40487404 | PMC:PMC12141247 | DOI:10.3389/fphar.2025.1584658

Front Pharmacol. 2025 May 22;16:1594032. doi: 10.3389/fphar.2025.1594032. eCollection 2025.

ABSTRACT

OBJECTIVE: To assess the feasibility and impact of incorporating a multidisciplinary pharmacogenomics (PGx) service within an underserved behavioral health clinic, with an emphasis on clinician perceptions.

METHODOLOGY: This study was conducted in two phases at the Texas A&M Family Care Clinic. Phase one involved an online cross-sectional survey of the multidisciplinary clinic team to assess their knowledge, attitudes, and readiness for PGx integration. Phase two detailed the development and implementation of a PGx service within the Integrated Behavioral Health (IBH) clinic, outlining the workflow and collaborative approach used to offer genetic testing to eligible patients.

KEY FINDINGS: Of the 23 survey participants, 91% believed the PGx service would positively impact patient care, and 87% expressed interest in receiving PGx-related training. Confidence in pharmacists' ability to lead the service was reported by 65% of respondents. The primary concerns identified included cost of care, clinical utility, and potential workflow disruptions. A collaborative implementation model was developed, including preemptive and reactive testing pathways.

CONCLUSION: The implementation of a pharmacist-driven PGx service in an underserved behavioral health clinic was well-received by the clinical team and deemed feasible. While concerns regarding resources and workflow were noted, strong interest in training and multidisciplinary collaboration highlights the potential for scalable PGx service models in similar settings.

PMID:40487400 | PMC:PMC12142042 | DOI:10.3389/fphar.2025.1594032

Glob Med Genet. 2025 May 6;12(3):100056. doi: 10.1016/j.gmg.2025.100056. eCollection 2025 Sep.

ABSTRACT

OBJECTIVE: We investigated the distribution of polymorphisms in five hypertension-related drug-target genes including cytochrome P450 2C9*3 (CYP2C9 *3), angiotensin II receptor type 1(AGTR1) (1166 A>C), cytochrome P450 2D6 * 10 (CYP2D6 *10), β1-adrenergic receptors (ADRB1) (1165 G>C), and angiotensin converting enzyme (ACE I/D) in patients with hypertension in Beijing. The study aimed to provide a theoretical basis that will guide the application of personalized hypertensive therapy in this population and develop more targeted prevention and treatment strategies for hypertension and other chronic disease in different regions.

MATERIALS AND METHODS: We retrospectively analyzed 317 patients with hypertension from Beijing who were admitted to Peking University People's Hospital from October 2021 to January 2024. The polymorphisms of five genes associated with Class A and B antihypertensive drugs were detected through real-time fluorescence PCR. In addition, we explored the distribution of different genotypes in the patient population while considering gender and comorbidities.

RESULTS: We obtained a significant difference in ADRB1(1165 G>C) between males and females, and the allele mutation frequency of ACE I/D was found to be higher in the Beijing population.

CONCLUSION: Most hypertensive patients in the Beijing region carry a high frequency of CYP2D6 * 10, ADRB1(1165 G>C), and ACE I/D genes, implying that they might be more sensitive to β-blockers, potentially benefitting more from ACEI drugs. The high allele frequencies of CYP2D6 * 10, ADRB1(1165 G>C), and ACE I/D in Beijing hypertensive patients indicate enhanced sensitivity to β-blockers and good therapeutic response to ACE inhibitors. Therefore, clinicians need to account for these factors when prescribing the aforementioned medications.

PMID:40487344 | PMC:PMC12145551 | DOI:10.1016/j.gmg.2025.100056

J Allergy Clin Immunol Glob. 2025 Apr 11;4(3):100470. doi: 10.1016/j.jacig.2025.100470. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: Although early-life respiratory illnesses (RIs) are linked to childhood asthma, it is unclear whether children are predisposed to both conditions or if RIs induce alterations that lead to asthma. Puerto Rican children, who bear a disproportionate burden of early-life RIs and asthma, are an important population for studying this relationship.

OBJECTIVE: We sought to describe the design and baseline characteristics of the Puerto Rican Infant Metagenomic and Epidemiologic Study of Respiratory Outcomes (PRIMERO) birth cohort.

METHODS: PRIMERO is designed to examine the role of respiratory viruses on the development of RIs and asthma. Pregnant women were recruited at Hospital Interamericano de Medicina Avanzada-San Pablo in Caguas, Puerto Rico. Questionnaires at birth and annual follow-ups gather clinical, social, and environmental data. Collected samples include postterm maternal blood; infant cord blood; the child's blood at year 2; and the child's nasal airway epithelium at birth, during RIs over the first 2 years, and annually until age 5.

RESULTS: We enrolled 2,100 mother-child dyads into the PRIMERO study between February 2020 and June 2023, representing 59% of births at Hospital Interamericano de Medicina Avanzada. As of April 29, 2024, 2,069 participants remain active, with high rates of biospecimen collection and annual visit participation. Illness surveillance detected 6,076 RIs, with 38.4% involving the lower respiratory tract.

CONCLUSION: The PRIMERO birth cohort study, with its comprehensive data on viral exposures, respiratory outcomes, and airway molecular phenotypes in a high-risk population of Puerto Rican children, is uniquely positioned to address long-standing questions about the early-life determinants and mechanisms underlying virus-related asthma development.

PMID:40486693 | PMC:PMC12140944 | DOI:10.1016/j.jacig.2025.100470

Cureus. 2025 May 8;17(5):e83731. doi: 10.7759/cureus.83731. eCollection 2025 May.

ABSTRACT

Managing heart failure (HF) presents ongoing challenges due to the varied nature of the condition among individuals. Recent shifts toward personalized care aim to move beyond standard treatments by considering the unique characteristics of each patient. This review brings together current ideas and advancements that could shape a more tailored approach to HF, offering insights into how patient-specific strategies might improve the care. However, fully embracing this approach requires overcoming several hurdles to ensure these innovations are practical and widely available.

PMID:40486428 | PMC:PMC12145133 | DOI:10.7759/cureus.83731

Gynecol Oncol. 2025 Jun 5;198:112-129. doi: 10.1016/j.ygyno.2025.05.013. Online ahead of print.

ABSTRACT

OBJECTIVE: Many epithelial ovarian cancer (EOC) risk factors relate to sex hormones. The association between these factors and the expression of androgen receptor (AR), estrogen receptor-α (ER), and progesterone receptor (PR) in tumors is unknown.

METHOD: We linked epidemiologic, AR/ER/PR tumor expression, and survival data from 19 studies in the Ovarian Cancer Association Consortium (OCAC; 4762 cases, 20,888 controls) and the Ovarian Tumor Tissue Analysis (OTTA) consortium (5737 cases). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) between hormonally-linked factors and tumor AR/ER/PR expression using polytomous logistic regression. We assessed survival by AR/ER/PR tumor expression overall and by histotype using Kaplan-Meier curves and Cox proportional hazards models.

RESULTS: Overweight/obesity was associated with higher risk of ER- tumors (OR:1.53, 95 % I:1.18-1.98). Hysterectomy was associated with greater risk of ER+ tumors (OR:4.99, 95 % CI:4.27-5.83), which varied by AR expression (Pheter=0.003). Postmenopause was associated with a higher risk of PR- tumors (OR 1.52, 95 % CI 1.26-1.83), which varied based by AR (Pheter < 0.001) and ER (Pheter < 0.001) expression. Gravidity, oral contraception duration, and breastfeeding duration showed differing dose-response relationships according to AR/ER/PR expression. Hormone therapy use, postmenopause, physical inactivity, and being obese/overweight prior to diagnosis were differentially associated with survival based on AR/ER/PR expression and histotype.

CONCLUSION: EOC has varying risk and prognostic profiles depending on both histotype and AR/ER/PR expression. Biological mechanisms underlying the association between hormonally-linked factors and EOC need to be studied by both histotypes and by AR, ER, and PR expression.

PMID:40482607 | DOI:10.1016/j.ygyno.2025.05.013

Nat Prod Res. 2025 Jun 6:1-25. doi: 10.1080/14786419.2025.2513583. Online ahead of print.

ABSTRACT

Herbal and plant-based medicines have been used for centuries for their therapeutic properties. However, understanding their pharmacokinetics is essential for optimising their efficacy, ensuring their safety and guiding appropriate dosing regimens. Herbal and plant-based medications can be ingested, inhaled, applied topically or injected. Factors such as solubility, formulation and interactions with gut enzymes and transporters influence their absorption characteristics. Distribution of these compounds involves their movement throughout the body, influenced by factors like blood flow, tissue permeability and plasma protein binding. Herbal and plant-based medications are metabolised in the liver by cytochrome P450 enzymes and conjugation routes. Metabolism can vary by genetics and gut microbiome. These compounds can be excreted by the kidneys, liver, faeces, lungs, sweat and saliva. This review aims to decode the pharmacokinetics of herbal and plant-based medicines by providing a comprehensive overview of their absorption, distribution, metabolism and elimination processes.

PMID:40481630 | DOI:10.1080/14786419.2025.2513583