COMT val158met moderation of dopaminergic drug effects on cognitive function: a critical review.

Pharmacogenomics J. 2016 May 31;

Authors: Schacht JP

Abstract
The relationship between dopamine (DA) tone in the prefrontal cortex (PFC) and PFC-dependent cognitive functions (for example, working memory, selective attention, executive function) may be described by an inverted-U-shaped function, in which both excessively high and low DA is associated with impairment. In the PFC, the COMT val158met single nucleotide polymorphism (rs4680) confers differences in catechol-O-methyltransferase (COMT) efficacy and DA tone, and individuals homozygous for the val allele display significantly reduced cortical DA. Many studies have investigated whether val158met genotype moderates the effects of dopaminergic drugs on PFC-dependent cognitive functions. A review of 25 such studies suggests evidence for this pharmacogenetic effect is mixed for stimulants and COMT inhibitors, which have greater effects on D1 receptors, and strong for antipsychotics, which have greater effects on D2 receptors. Overall, COMT val158met genotype represents an enticing target for identifying individuals who are more likely to respond positively to dopaminergic drugs.The Pharmacogenomics Journal advance online publication, 31 May 2016; doi:10.1038/tpj.2016.43.

PMID: 27241058 [PubMed - as supplied by publisher]

Anti-tumor necrosis factor-α therapy in uveitis.

Surv Ophthalmol. 2015 Nov-Dec;60(6):575-89

Authors: Cordero-Coma M, Sobrin L

Abstract
Since the first reported use in 2001 of an anti-tumor necrosis factor-alpha (TNF-α) agent, infliximab, for the treatment of uveitis, several new anti-TNF-α agents have emerged for the treatment of refractory noninfectious uveitides, although their use remains off-label in the US. These agents have demonstrated remarkable clinical antiinflammatory efficacy and a potential immunoregulatory role in selected uveitis patients, but it is currently unclear whether they can modify the natural history of disease. We review the rationale and clinical indications for this therapy, the differences between agents, how to manage dosing and intervals, and how to screen for and identify potential side effects. We also present a summary of the science behind the use of anti-TNF-α agents in ocular inflammation and the evidence for their efficacy.

PMID: 26164735 [PubMed - indexed for MEDLINE]

SLCO1B1*5 polymorphism (rs4149056) is associated with chemotherapy-induced amenorrhea in premenopausal women with breast cancer: a prospective cohort study.

BMC Cancer. 2016;16(1):337

Authors: Reimer T, Kempert S, Gerber B, Thiesen HJ, Hartmann S, Koczan D

Abstract
BACKGROUND: Because inheritance is recognized as playing a role in age at menarche and natural menopause, the development of chemotherapy-induced amenorrhea (CIA) might depend on inherited genetic factors; however, studies that explore such a correlation are few and have received scant attention. Given the importance of this topic we conducted a comprehensive genotype study in young women (≤45 years) with early-stage breast cancer.
METHODS: Our approach tested the effect of variant polymorphisms in drug metabolism enzymes (DMEs) using a predesigned pharmacogenomics panel (TaqMan® OpenArray®, Life Technologies GmbH, Darmstadt, Germany) in premenopausal women (n = 50). Patients received contemporary chemotherapy; in all cases a cyclophosphamide-based regimen with a dose of at least 500 mg/m(2) for six cycles. CIA was considered to be present in women with no resumption of menstrual bleeding within 12 months after completion of chemotherapy or goserelin.
RESULTS: Twenty-six patients (52 %) showed CIA during follow-up whereas 24 women (48 %) remained premenopausal. Of all the DMEs studied, only the SLCO1B1*5 (rs4149056) genotype was associated with the development of CIA (P = 0.017). Of the 26 patients who were homozygous for the T/T allele SLCO1B1*5, 18 (69.2 %) developed CIA compared with 8 (30.8 %) of the 22 patients who were heterozygous (C/T allele). The association of heterozygous SLCO1B1*5 allele (OR 0.038; 95%CI: 0.05-0.92) with a lower risk of developing CIA remained significant in a binary logistic regression analysis that include age, SLCO1B1*5 allele variants, and goserelin therapy.
CONCLUSIONS: Patient age and SLCO1B1*5 allele variants predict the likelihood of young women with breast cancer developing CIA.

PMID: 27234217 [PubMed - as supplied by publisher]

Genetic polymorphisms of pharmacogenomic VIP variants in the Mongol of Northwestern China.

BMC Genet. 2016;17(1):70

Authors: Jin T, Shi X, Wang L, Wang H, Feng T, Kang L

Abstract
BACKGROUND: Within a population, the differences of pharmacogenomic variant frequencies may produce diversities in drug efficacy, safety, and the risk associated with adverse drug reactions. With the development of pharmacogenomics, widespread genetic research on drug metabolism has been conducted on major populations, but less is known about minorities.
RESULTS: In this study, we recruited 100 unrelated, healthy Mongol adults from Xinjiang and genotyped 85 VIP variants from the PharmGKB database. We compared our data with eleven populations listed in 1000 genomes project and HapMap database. We used χ(2) tests to identify significantly different loci between these populations. We downloaded SNP allele frequencies from the ALlele FREquency Database to observe the global genetic variation distribution for these specific loci. And then we used Structure software to perform the genetic structure analysis of 12 populations.
CONCLUSIONS: Our results demonstrated that different polymorphic allele frequencies exist between different nationalities,and indicated Mongol is most similar to Chinese populations, followed by JPT. This information on the Mongol population complements the existing pharmacogenomic data and provides a theoretical basis for screening and therapy in the different ethnic groups within Xinjiang.

PMID: 27233804 [PubMed - as supplied by publisher]

UGT1A6- and UGT2B7-related valproic acid pharmacogenomics according to age groups and total drug concentration levels.

Pharmacogenomics. 2016 May 27;

Authors: Chatzistefanidis D, Lazaros L, Giaka K, Nakou I, Tzoufi M, Georgiou I, Kyritsis A, Markoula S

Abstract
AIM: The role of UGT1A6 and UGT2B7 polymorphisms and the impact of total drug plasma concentration in valproic acid (VPA) pharmacogenomics.
PATIENTS & METHODS: A total of 134 Greek patients were recruited (76 adults). Patients were genotyped for UGT1A6 19T>G, 541A>G and 552A>C and UGT2B7 802T>C polymorphisms. Patients' demographic and clinical data were registered. Natural logarithm of concentration-to-dose ratio (CDR) was also calculated as the final outcome.
RESULTS: No significant genotype-related differences in VPA metabolism were noted among various subgroups. An increased lnCDR ratio was noted in children patients compared with adults suggesting increased metabolic capability in younger ages.
CONCLUSION: UGT1A6 and UGT2B7 genotypes were not related to significant changes in VPA metabolism, even after controlling for total drug concentration levels. Younger ages were associated with increased VPA clearance rate.

PMID: 27232006 [PubMed - as supplied by publisher]

P2Y12-ADP receptor antagonists: Days of future and past.

World J Cardiol. 2016 May 26;8(5):327-32

Authors: Laine M, Paganelli F, Bonello L

Abstract
Antiplatelet therapy is the cornerstone of the therapeutic arsenal in coronary artery disease. Thanks to a better understanding in physiology, pharmacology and pharmacogenomics huge progress were made in the field of platelet reactivity inhibition thus allowing the expansion of percutaneous coronary intervention. Stent implantation requires the combination of two antiplatelet agents acting in a synergistic way. Asprin inhibit the cyclo-oxygenase pathway of platelet activation while clopidogrel is a P2Y12 adenosine diphosphate (ADP)-receptor antagonist. This dual antiplatelet therapy has dramatically improved the prognosis of stented patients. However, due to pharmacological limitations of clopidogrel (interindividual variability in its biological efficacy, slow onset of action, mild platelet reactivity inhibition) ischemic recurrences remained high following stent implantation especially in acute coronary syndrome patients. Thus, more potent P2Y12-ADP receptor inhibitors were developped including prasugrel, ticagrelor and more recently cangrelor to overcome these pitfalls. These new agents reduced the rate of thrombotic events in acute coronary syndrome patients at the cost of an increased bleeding risk. The abundance in antiplatelet agents allow us to tailor our strategy based on the thrombotic/bleeding profile of each patient. Recently, the ACCOAST trial cast a doubt on the benefit of pre treatment in non-ST segment elevation acute coronary syndrome. The aim of the present review is to summarize the results of the main studies dealing with antiplatelet therapy in stented/acute coronary syndromes patients.

PMID: 27231519 [PubMed]

Cytotoxicity of Salvia miltiorrhiza Against Multidrug-Resistant Cancer Cells.

Am J Chin Med. 2016 May 24;:1-24

Authors: Wu CF, Bohnert S, Thines E, Efferth T

Abstract
Salvia miltiorrhiza Bunge (Lamiaceae) is a well-known Chinese herb that possesses numerous therapeutic activities, including anticancer effects. In this study, the cytotoxicity and the biological mechanisms of S. miltiorrhiza (SM) root extract on diverse resistant and sensitive cancer cell lines were investigated. CEM/ADR5000 cells were 1.68-fold resistant to CCRF-CEM cells, while HCT116 (p53[Formula: see text] and U87.MG[Formula: see text]EGFR cells were hypersensitive (collateral sensitive) compared to their parental cells. SM root extract stimulated ROS generation, cell cycle S phase arrest and apoptosis. The induction of the intrinsic apoptotic pathway was validated by increased cleavage of caspase 3, 7, 9 and poly ADP-ribose polymerase (PARP). MAP kinases including JNK, ERK1/2 and p38 were obviously phosphorylated and nuclear P65 was downregulated upon SM treatment. Transcriptome-wide COMPARE analysis revealed that the expression of encoding genes with diverse functions were associated with the cellular response to cryptotanshinone, one of the main constituents of SM root extract. In conclusion, SM root extract exerted profound cytotoxicity towards various sensitive and resistant cancer cells and induced the intrinsic apoptotic pathway.

PMID: 27222067 [PubMed - as supplied by publisher]

Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy.

Pharmacogenomics J. 2016 May 24;

Authors: Zur RM, Roy LM, Ito S, Beyene J, Carew C, Ungar WJ

Abstract
Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3-87.0%) and 98.9% (96.3-100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1-99.4%) and 100.0% (99.9-100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4-95.5%) and 92.6% (86.5-96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6-97.5%) and 99.2% (98.4-99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.37.

PMID: 27217052 [PubMed - as supplied by publisher]

Clinical-pharmacogenetic predictive models for MTX discontinuation due to adverse events in rheumatoid arthritis.

Pharmacogenomics J. 2016 May 24;

Authors: Jenko B, Lusa L, Tomsic M, Praprotnik S, Dolzan V

Abstract
We describe a novel approach to investigate and evaluate combined effect of a large number of clinical and pharmacogenetic factors on treatment outcome. We have used this approach to investigate predictors of methotrexate (MTX)-induced adverse events (AEs) leading to treatment discontinuation in rheumatoid arthritis (RA) patients. In total, 333 RA patients were genotyped for 34 polymorphisms in MTX transporters, folate and adenosine pathways. The effect of clinical and pharmacogenetic factors was assessed with penalized regression in the cause-specific Cox proportional hazards model. The predictive capacity was evaluated with the area under time-dependent receiver operating characteristic curve where cross-validation was applied. SLC19A1, ABCG2, ADORA3 and TYMS were associated with discontinuation because of AEs in clinical-pharmacogenetic model. Cross-validation showed that both clinical-pharmacogenetic model and nongenetic model had worthless predictive ability for MTX discontinuation because of AEs. These models could be further improved, either with additional polymorphisms or with epigenetic predictors.The Pharmacogenomics Journal advance online publication, 24 May 2016; doi:10.1038/tpj.2016.36.

PMID: 27217051 [PubMed - as supplied by publisher]

Implementing Pharmacogenomics at Your Institution: Establishment and Overcoming Implementation Challenges.

Clin Transl Sci. 2016 May 23;

Authors: Arwood MJ, Chumnumwat S, Cavallari LH, Nutescu EA, Duarte JD

Abstract
With advancements in pharmacogenomics research and genotyping technology, implementation of pharmacogenomics into clinical practice is now feasible. The aim of this publication is to serve as a tutorial for institutions interested in developing pharmacogenomics services. Topics covered include resources needed, clinical decision support establishment, choosing a genotyping platform, and challenges faced with pharmacogenomics service implementation. This tutorial provides practical advice, drawing upon experience of two established clinical pharmacogenomics services. This article is protected by copyright. All rights reserved.

PMID: 27214750 [PubMed - as supplied by publisher]

Exome Sequencing of Extreme Clopidogrel Response Phenotypes Identifies B4GALT2 as a Determinant of On-treatment Platelet Reactivity.

Clin Pharmacol Ther. 2016 May 23;

Authors: Scott SA, Collet JP, Baber U, Yang Y, Peter I, Linderman M, Sload J, Qiao W, Kini AS, Sharma SK, Desnick RJ, Fuster V, Hajjar RJ, Montalescot G, Hulot JS

Abstract
Interindividual variability in platelet aggregation is common among patients treated with clopidogrel, and both high and low (LTPR) on-treatment platelet reactivity increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, coronary artery disease (CAD) patients with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n=636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRU; p=0.0077) and residual platelet aggregation (p=0.0008) compared to non-carriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (p=0.0298) and replication (n=160; PRU: p=0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion. This article is protected by copyright. All rights reserved.

PMID: 27213804 [PubMed - as supplied by publisher]

Adenosine Hypothesis of Antipsychotic Drugs Revisited: Pharmacogenomics Variation in Nonacute Schizophrenia.

OMICS. 2016 May;20(5):283-289

Authors: Turčin A, Dolžan V, Porcelli S, Serretti A, Plesničar BK

Abstract
The existing antipsychotic therapy is based on dopamine hyperfunction and glutamate hypofunction hypotheses of schizophrenia. Adenosine receptors (ADORA) have a neuromodulatory role and can control dopaminergic and glutamatergic systems. To elucidate the effect of ADORA polymorphisms on psychopathological symptoms and adverse effects in patients with schizophrenia on long-term antipsychotic treatment, we examined 127 nonacute schizophrenia outpatients in a cross-sectional study using the Positive and Negative Symptoms Scale, Simpson-Angus Scale, Barnes Akathisia Rating Scale, and Abnormal Involuntary Movement Scale. All patients were genotyped for 18 polymorphisms in ADORA1, ADORA2A, and ADORA3. We found an association between ADORA1 rs3766566 and psychopathological symptoms (p = 0.006), in particular, with positive psychopathological symptoms (p = 0.010) and general psychopathological symptoms (p = 0.023), between ADORA2A rs2298383 and general psychopathological symptoms (p = 0.046), and between ADORA2A rs5751876 and akathisia (p = 0.015). Haplotype analysis showed an association between ADORA1 CTCAACG haplotype and overall psychopathological symptoms (p = 0.019), positive psychopathological symptoms (p = 0.021), and akathisia (p = 0.028). ADORA2A TCCTC haplotype was associated with parkinsonism (p = 0.014). ADORA3 CACTAC was associated with akathisia (p = 0.042), whereas CACTAT was associated with akathisia (p = 0.045) and tardive dyskinesia (p = 0.023). The results of this first comprehensive study on ADORA polymorphisms in patients with nonacute schizophrenia receiving long-term antipsychotic therapy suggest an important neuromodulatory role of ADORA receptors in both psychopathological symptoms and adverse effects of antipsychotics.

PMID: 27195966 [PubMed - as supplied by publisher]

Genome-Wide Association Study of Absolute QRS Voltage Identifies Common Variants of TBX3 as Genetic Determinants of Left Ventricular Mass in a Healthy Japanese Population.

PLoS One. 2016;11(5):e0155550

Authors: Sano M, Kamitsuji S, Kamatani N, Tabara Y, Kawaguchi T, Matsuda F, Yamagishi H, Fukuda K, Japan Pharmacogenomics Data Science Consortium (JPDSC)

Abstract
Left ventricular hypertrophy (LVH) represents a common final pathway leading to heart failure. We have searched for genetic determinants of left ventricular (LV) mass using values for absolute electrocardiographic QRS voltage in a healthy Japanese population. After adjusting for covariates, the corrected S and R wave voltages in leads V1 and V5 from 2,994 healthy volunteers in the Japan Pharmacogenomics Data Science Consortium (JPDSC) database were subjected to a genome-wide association study. Potential associations were validated by an in silico replication study using an independent Japanese population obtained from the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. We identified a novel association between the lead V5, R wave voltage in Japanese individuals and SNP rs7301743[G], which maps near the gene encoding T-box transcription factor Tbx3. Meta-analysis of two independent Japanese datasets demonstrated a marginally significant association of SNP rs7301743 in TBX3|MED13L with a 0.071 mV (95% CI, 0.038-0.11 mV) shorter R wave amplitude in the V5 lead per minor allele copy (P = 7.635 x 10-8). The transcriptional repressor, TBX3, is proposed to suppress the development of working ventricular myocardium. Our findings suggest that genetic variation of Tbx3 is associated with LV mass in a healthy Japanese population.

PMID: 27195777 [PubMed - as supplied by publisher]

Genotyping NUDT15 can predict the dose reduction of 6-MP for children with acute lymphoblastic leukemia especially at a preschool age.

J Hum Genet. 2016 May 19;

Authors: Suzuki H, Fukushima H, Suzuki R, Hosaka S, Yamaki Y, Kobayashi C, Sakai A, Imagawa K, Iwabuchi A, Yoshimi A, Nakao T, Kato K, Tsuchida M, Kiyokawa N, Koike K, Noguchi E, Fukushima T, Sumazaki R

Abstract
The pharmacokinetics among children has been altered dynamically. The difference between children and adults is caused by immaturity in things such as metabolic enzymes and transport proteins. The periods when these alterations happen vary from a few days to some years after birth. We hypothesized that the effect of gene polymorphisms associated with the dose of medicine could be influenced by age. In this study, we analyzed 51 patients with childhood acute lymphoblastic leukemia (ALL) retrospectively. We examined the associations between the polymorphism in NUDT15 and clinical data, especially the dose of 6-mercaptopurine (6-MP). Ten of the patients were heterozygous for the variant allele in NUDT15. In patients under 7 years old with NUDT15 variant allele, the average administered dose of 6-MP was lower than that for the patients homozygous for the wild-type allele (P=0.04). Genotyping of NUDT15 could be a beneficial to estimate the tolerated dose of 6-MP for patients with childhood ALL, especially at a preschool age in Japan. Furthermore, the analysis with stratification by age might be useful in pharmacogenomics among children.Journal of Human Genetics advance online publication, 19 May 2016; doi:10.1038/jhg.2016.55.

PMID: 27193222 [PubMed - as supplied by publisher]

Exploiting microRNA Specificity and Selectivity: Paving a Sustainable Path Towards Precision Medicine.

Adv Exp Med Biol. 2015;888:1-3

Authors: Santulli G

Abstract
In his State of the Union address before both chambers of the US Congress, President Barack Obama called for increased investment in US infrastructure and research and announced the launch of a new Precision Medicine Initiative, aiming to accelerate biomedical discovery. Due to their well-established selectivity and specificity, microRNAs can represent a useful tool, both in diagnosis and therapy, in forging the path towards the achievement of precision medicine. This introductory chapter represents a guide for the Reader in examining the functional roles of microRNAs in the most diverse aspects of clinical practice, which will be explored in this third volume of the microRNA trilogy.

PMID: 26663175 [PubMed - indexed for MEDLINE]

Editorial.

Cell Mol Biol (Noisy-le-grand). 2016;62(5):1

Authors: Farooqi AA

Abstract
To optimize treatment, we need to understand biology of different diseases in much more detail with emphasis on morphological, proteomic, genetic and epigenetic grounds. Keeping in view the facts and stimulating developments in molecular pathology, it is worthwhile to present an up-date on this topic.It is becoming progressively more understandable that exciting fields of pharmacogenomics and pharmacogenetics have revolutionized field of medicine. Better understanding of underlying mechanisms of different diseases has provided us with better ways to treat illnesses. There cannot be a distinct definition of 'discipline' of pathology, mainly because investigation of human disease encompasses all the scientific disciplines of biomedical research. Sen et al reported that hyperbarıc oxygen (HBO) administration affected the endocrinological functions of fat tissue. Observation of significant increases in leptin, visfatin and IL-10 levels, leads to the consideration that in near future HBO administration may be applied as treatment for obesity, DM, eating disorders and obesity related diseases...

PMID: 27188861 [PubMed - as supplied by publisher]

Hepatotoxicity of targeted therapy for cancer.

Expert Opin Drug Metab Toxicol. 2016 May 17;

Authors: Lee KW, Chan SL

Abstract
Molecular targeted agents (MTA) have become the mainstay of treatment for many cancers in the past decade. Hepatotoxicity of varying forms and severity is common with the use of MTA and risk factors have been identified. Hepatotoxicity can result from direct hepatocellular, cholestatic or steatotic injury, through immunogenic pathways or reactivation of viral hepatitis. Selecting an appropriate starting dose for special populations, arranging viral hepatitis screening prior to initiation of relevant MTA and knowing the standards for liver function test (LFT) monitoring are crucial to preventing morbidity and mortality from drug-induced liver injury (DILI) and minimising discontinuation of MTA. This is a comprehensive review on how to interpret LFTs in the light of MTA use, mechanisms of DILI, identification of high risk groups, and measures for preventing and managing hepatotoxicity.
INTRODUCTION: Understanding the mechanism of DILI with MTA, and how to avoid and manage these toxicities is essential for minimising inferior cancer treatment outcomes. An organised and comprehensive overview of MTA-associated hepatotoxicity is lacking; this review aims to fill the gap. Areas covered: A literature review was performed based on published case reports and relevant studies or articles pertaining to the topics on PubMed. Food and Drug Administration drug information documents and search on the US National Library of Medicine LiverTox database was performed for all relevant MTA. Expert opinion: MTA-associated hepatotoxicity is common but rarely fatal. The pattern of hepatotoxicity is predominantly idiosyncratic. Pharmacogenomics show potential in predicting patients at risk of poorly metabolising or developing immunoallergic responses to MTA, but prospective data is scant. Preventing reactivation of viral hepatitis using anti-viral drugs, and avoidance of drug combinations at high risk of negative interactions are the most readily preventable measures for DILI.

PMID: 27187715 [PubMed - as supplied by publisher]

Clinical Zheng-hou Pharmacology: the Missing Link between Pharmacogenomics and Personalized Medicine?

Curr Vasc Pharmacol. 2015;13(4):423-32

Authors: Yu YN, Liu J, Zhang L, Wang Z, Duan DD, Wang YY

Abstract
In Chinese medicine, Zheng-hou, instead of disease, is used to define complex medical problems in clinical practice. In the postgenomics era, it becomes particularly compelling to review the application of Zheng-hou in characterizing complex clinical problems independent of disease or syndrome. While disease or syndrome describes a pathological phenotype or phenotypes, Zheng-hou spells the pathological phenome. Clinical Zheng-hou pharmacology (CZP) is an emerging clinical discipline that aims to leverage breakthroughs in the genome-wide solutions for complex medical problems through a combination of the current "omics" technology and the knowledge of Chinese medicine. The concept of CZP suggests that systematic and standard studies of multiple phenotypes will be important because of the collaborative cross between diversified external and internal factors at different levels both in vitro and in vivo. In this paper, we discuss the novel phenomic approaches to the understanding of Zheng-hou and the link of pharmacogenomics to personalized medicine through CZP, or pharmacophenomics. CZP enables ever-finer mapping of Zheng-hou and detection of dynamic variations in most current omics platforms. Although major challenges still remain in identifying and effectively investigating the diversity of Zheng-hou, CZP is expected to pave new paths to the systemic understanding of medical problems. While still at early stages in the clinical phenome domain, there remains great promise that CZP can help us realize the application of personalized medicine and contribute to rational holistic diagnosis and treatment.

PMID: 25360846 [PubMed - indexed for MEDLINE]

Genetic testing to guide warfarin dosing: Impact of direct oral anticoagulants.

Clin Pharmacol Ther. 2016 May 14;

Authors: Lentz SR

PMID: 27178490 [PubMed - as supplied by publisher]

Therapeutic Application of Pharmacogenomics in Oncology.

AAPS J. 2016 May 13;

Authors: Zhang Y, Somtakoune SD, Cheung C, Listiawan M, Feng X

Abstract
Personalizing cancer treatment has been proved to be difficult for healthcare providers due to the nature of chemotherapies which includes narrow therapeutic indices, severe and potential life-threatening toxicities, and variable response rates and efficacies. Studies in pharmacogenomics (PGx) may help guide clinicians to personalize treatment for cancer patients. Implementing PGx in cancer treatment may offer choices to anticipate differences in drug response, resistance, efficacy, and toxicity within chemotherapeutic agents and targeted immune biologic agents. This can be used to achieve optimization of treatment regimens based on patients' variability. Many of the cancer treatment agents are biologics targeting specific antigens expressed on cancer cells, or blocking stimulators and signal transduction pathways of tumor growth, or enhance anticancer immune responses. It is now crucial for clinicians to understand the important association of clinically important biomarker polymorphisms with the clinical benefits of cancer therapies. By identifying specific PGx biomarker polymorphisms present in cancer cells, physicians can select and tailor a patient's treatment based on his or her genetic profile. PGx-guided cancer treatment may have the ability to improve the survival of patients while avoiding the unnecessary cost due to unresponsive treatment and toxicities of that patients experience.

PMID: 27178043 [PubMed - as supplied by publisher]