Pharmacometabonomics, as an emerging branch of system biology, has been increasingly used in personalized medicine and showed broad prospects. By means of metabonomics, the complicated and detailed metabolic profile of the patient is described, thus providing more detailed description of the disease phenotype. With this understanding, response of different individuals to the drugs are predicted or evaluated through inherent genetic information of the individual combined with the environmental factors. As a result, appropriate drugs and dosage are chosen, which greatly promotes the realization of the individualized therapy goals. This article describes the emerging field of pharmacometabonomics, and the research results of personalized medicine based on the pharmacometabonomics in recent years are reviewed in detail.
Humans ; Metabolome ; Metabolomics ; Pharmacogenetics ; Precision Medicine ; methods

The effective and toxic ranges of anticancer drugs are very narrow and, in some cases, inverted. Thus determination of the most appropriate dosage and schedule of administration is crucial for optimal chemotherapy. In common arm trials conducted in Japan and by Southwest Oncology Group (SWOG) that used the same doses and schedules for the administration of carboplatin plus paclitaxel, the frequency of hematological toxicity was significantly higher in the Japanese trials than in the SWOG trial, despite demonstrating similar response rates. The frequency of epidermal growth factor receptor (EGFR) mutations in tumors was significantly higher among East Asian populations, and these populations are also reported to demonstrate a higher response rates to epidermal growth factor receptor tyrosine-kinase inhibitors (EGFR-TKIs). The prevalence of interstitial lung disease induced by treatment with EGFR-TKIs has been shown to be quite high in the Japanese population. Clinical trials of cetuximab against non-small cell lung cancer and of bevacizumab against stomach cancer have shown that these agents are only active in Caucasians. In a trial examining the use of sorafenib after transarterial chemoembolization in Korean and Japanese patients with advanced hepatocellular carcinoma, the compliance and dose intensity of the drug were quite low compared with other trials. Although not only identified pharmacogenomics differences but also differences in social environment, and regional medical care, including pharmacoeconomics strongly influence ethnic differences in treatment response, further identification and understanding of the pharmacogenomics underlying ethnic differences will be essential to timely and reliable global development of new anticancer drugs.
Antineoplastic Combined Chemotherapy Protocols/adverse effects/*therapeutic use ; Asian Continental Ancestry Group ; Carcinoma, Non-Small-Cell Lung/drug therapy/ethnology ; Chemoembolization, Therapeutic ; Clinical Trials as Topic ; Drug Design ; Ethnic Groups ; Humans ; Japan ; Lung Diseases, Interstitial/chemically induced ; Lung Neoplasms/drug therapy/ethnology ; Mutation ; Pharmacogenetics/*methods ; Receptor, Epidermal Growth Factor/genetics ; Republic of Korea

PURPOSE: The purpose of this study was to determine the pharmacogenetic effects of complement factor H (CFH) Y402H, LOC387715 and high-temperature requirement factor A1 (HTRA1) genotypes on the treatment of exudative age-related macular degeneration (AMD) by intravitreal bevacizumab injection in a Korean population. METHODS: Seventy-five patients diagnosed with exudative AMD were treated with intravitreal bevacizumab (2.5 mg) monotherapy. All patients received three initial intravitreal bevacizumab injections every four weeks and were then treated "as needed" based on clinical findings, optical coherence tomography and fluorescein angiography during the 12 month follow-up period after the third injection. RESULTS: The difference in visual acuity improvement among the three genotypes of LOC387715 were statistically significant at six months post-treatment (logarithm of the minimum angle of resolution; TT, 0.346; GT, 0.264; GG, 0.188; p = 0.037). Among the LOC387715 genotypes, the number of additional injections was lower in patients who had the risk T allele (GG, 2.143; GT, 2.000; TT, 1.575; p = 0.064). There was no significant difference between visual acuity and central macular thickness change in the CFH Y402H polymorphism group during the 12 month follow-up period. However, the TC group of CFH Y402H required more additional bevacizumab injections than the TT group (TT, 1.517; TC, 3.363; p = 0.020). CONCLUSIONS: This study demonstrated that different LOC387715/HTRA1 genotypes resulted in different bevacizumab treatment responses on exudative AMD. Patients with the risk allele had an improved treatment response and less need for additional injections. However, patients with the CFH Y402H risk allele needed more additional injections of bevacizumab in order to improve visual acuity. This study illustrates how pharmacogenetic factors may help determine treatment modality and dosing. This could ultimately provide basic data for 'personalized medicine' in AMD.
Aged ; Alleles ; Angiogenesis Inhibitors/administration & dosage/therapeutic use ; Antibodies, Monoclonal, Humanized/*administration & dosage/therapeutic use ; DNA/*genetics ; Female ; Follow-Up Studies ; Genotype ; Humans ; Intravitreal Injections ; Macular Degeneration/drug therapy/epidemiology/*genetics ; Male ; Pharmacogenetics/*methods ; *Polymorphism, Genetic ; Retrospective Studies ; Serine Endopeptidases/*genetics/metabolism ; Vascular Endothelial Growth Factor A/antagonists & inhibitors ; Visual Acuity

Pharmacogenetics and pharmacogenomics are promising fields that will enable personalized therapy. However, one of the most important issues to be conquered in the practice of personalized medicine is the translation of scientific discoveries into better therapeutic outcomes. The international pharmacogenetic and pharmacogenomic approaches made in the field of personalized medicine and drug discovery are summarized in this review.
Drug Discovery ; methods ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Humans ; Pharmacogenetics ; methods ; Precision Medicine ; methods ; Translational Medical Research ; methods

There have been several success stories in the field of pharmacogenetics in recent years, including the analysis of HER2 amplification for trastuzumab selection in breast cancer and VKORC1 genotyping for warfarin dosing in thrombosis. Encouraging results from these studies suggest that genetic factors may indeed be important determinants of drug response and toxicity for at least some drugs. However, to apply pharmacogenetics appropriately, a thorough understanding of the scope and limitations of this field is required. The challenges include an appreciation of biological variability, logistical issues pertaining to the proper management of information, the need for robust methods and adequate sample quality with well-designed workflows. At the same time, the economics of pharmacogenetic testing from the perspective of clinicians, patients, governments, insurance companies and pharmaceutical companies will play an important role in determining its future use. Ethical considerations such as informed consent and patient privacy, as well as the role of regulatory bodies in addressing these issues, must be fully understood. Only once these issues are properly dealt with can the full benefits of pharmacogenetics begin to be realised.
Antineoplastic Agents ; pharmacology ; Genetic Privacy ; ethics ; Humans ; Informed Consent ; Neoplasms ; drug therapy ; Pharmacogenetics ; ethics ; methods ; Translational Medical Research ; methods

In addition to 6-mercaptopurine, 5-fluorouracil and irinotecan, the United States Food and Drug Administration (US FDA) has recently recommended label change for tamoxifen, to include pharmacogenetic information on treatment outcome. With the increasing availability of pharmacogenetic testing, on germline as well as somatic mutations, oncologists are now able to identify individuals at risk of severe treatment toxicity or poor treatment response. However, there are still knowledge gaps to fill before rationalised therapy based on pharmacogenetics can be fully integrated into clinical practice. This review provides an overview on the application of pharmacogenetic testing for germ line mutations in oncology to predict response and toxicity.
Antineoplastic Agents ; therapeutic use ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Genetic Testing ; methods ; Genotype ; Germ Cells ; drug effects ; Humans ; Neoplasms ; drug therapy ; genetics ; Pharmacogenetics ; methods ; Treatment Outcome

Humans ; Medical Oncology ; Neoplasms ; drug therapy ; genetics ; Pharmacogenetics ; methods

Disease Progression ; Humans ; Pharmacogenetics ; methods ; Precision Medicine ; methods ; Psoriasis ; genetics

Chemogenomics/chemical genomics has been widely used in novel drug research and discovery. Firstly, the concept of chemogenomics was introduced briefly. Secondly, we reviewed the progress of novel drug research and discovery based on forward chemogenomics, reverse chemogenomics and predictive chemogenomics. Finally, we showed progress of the research that chemogenomics has been used to novel drug research and discovery in pharmaceuticals companies.
Animals ; Drug Delivery Systems ; Drug Discovery ; methods ; Drug Industry ; trends ; Genomics ; methods ; Humans ; Pharmacogenetics ; methods

The mechanism of Chinese medications have some characteristic such as multi-pathway, multi-components, multi-targets and so on, which decide the direction of systems research. In the recent years, microarrays be concerned with the relative field of Chinese medications for its superiority of highthough, parallel and high-density. This paper mainly generalize the approach of these methods in the recent three years, such as finding effective target of Chinese medications, effective part of Chinese medications, checkup of Chinese medications, screening new drugs and so on. We suggest the concept of Pharmacogenomics of Chinese medications with the guidance of the theory of Chinese medications for further development of Chinese medications.
Animals ; Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; metabolism ; pharmacology ; Gene Expression Profiling ; Genomics ; methods ; Humans ; Models, Theoretical ; Oligonucleotide Array Sequence Analysis ; Pharmacogenetics ; methods ; Plants, Medicinal ; chemistry ; genetics ; metabolism