Pharmacogenomics: The Right Drug to the Right Person

Aneesh, T P; Miraj, Sonal Sekhar; Asha, Jose; Chandran, Lekshmi R.; Zachariah, Subin Mary

doi:10.4021/jocmr2009.08.1255

Cited by 46 publications

(23 citation statements)

References 7 publications

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“…The patients are commonly diagnosed lately with advanced disease. In spite of high response rates to the standard first-line treatment for advanced disease with primary debulking surgery, followed by cisplatin (DDP)-based chemotherapy, more than 70% of the patients eventually relapse developing drug-resistant disease [ 3 ]. In addition, although patients may respond firstly to the therapy, the cancer often becomes resistant to further chemotherapy, at this point, the number of effective treatment options is limited.…”

Section: Introductionmentioning

confidence: 99%

eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation

Zhang

Tian

et al. 2015

Oncotarget

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The eukaryotic translation initiation factor 3a (eIF3a) is one of the core subunits of the translation initiation complex eIF3, responsible for ribosomal subunit joining and mRNA recruitment to the ribosome. Our previous study identified that it was correlated with platinum response in lung cancer. The current study aims to test the hypothesis that eIF3a may affect the drug response and prognosis of ovarian cancer patients receiving platinum-based chemotherapy by regulating xeroderma pigmentosum complementation group C (XPC) and p27Kip1. Immunohistochemistry and western blot was used to determine the expression of eIF3a in 126 human ovarian cancer tissues followed by association analysis of eIF3a expression with patient's response and survival. Ectopic over-expression and RNA interference knockdown of eIF3a were carried out in A2780/cisplatin (DDP) and its parental A2780 cells, respectively, to determine the effect of altered eIF3a expression on cellular response to cisplatin by employing MTT assay. Western Blot analyses were also carried out to determine the regulation of eIF3a on XPC and p27Kip1. eIF3a expression was associated with response of ovarian cancer patients to DDP-based chemotherapy and their survival. Overexpression and knockdown of eIF3a increased and decreased the cellular response to cisplatin in A2780/DDP and A2780 cells, respectively. In addition, XPC and p27Kip1 were down regulated by eIF3a. eIF3a improves ovarian cancer patients' response to DDP-based chemotherapy via down regulating XPC and p27Kip1.

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Section: Introductionmentioning

confidence: 99%

eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation

Zhang

Tian

et al. 2015

Oncotarget

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“…Knowing all of the genes involved in drug response and understanding an individual's genetic make-up, can help to develop genetic tests that could predict a person's response to a particular drug and create personalized drugs with greater efficacy and safety. [ 54 , 55 ]…”

Section: Discussionmentioning

confidence: 99%

Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes

et al. 2018

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Background:Metformin is one of the most commonly used drugs for the treatment of type 2 diabetes mellitus (T2DM). Despite its widespread use, there are considerable interindividual variations in metformin response, with about 35% of patients failing to achieve initial glycemic control. These variabilities that reflect phenotypic differences in drug disposition and action may indeed be due to polymorphisms in genes that regulate pharmacokinetics and pharmacodynamics of metformin. Moreover, interethnic differences in drug responses in some cases correspond to substantial differences in the frequencies of the associated pharmacogenomics risk allele.Aim:This study aims to highlight and summarize the overall effects of organic cation transporter 1(OCT1) polymorphisms on therapeutic responses to metformin and to evaluate the potential role of such polymorphisms in interethnic differences in metformin therapy.Methods:We conducted a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. We searched for PubMed/MEDLINE, Embase, and CINAHL, relevant studies reporting the effects of OCT1 polymorphisms on metformin therapy in T2DM individuals. Data were extracted on study design, population characteristics, relevant polymorphisms, measure of genetic association, and outcomes. The presence of gastrointestinal side effects, glycated hemoglobin A1 (HbA1c) levels, fasting plasma glucose (FPG), and postprandial plasma glucose (PPG) concentrations after treatment with metformin were chosen as measures of the metformin responses. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO).Results:According to the data extracted, a total of 34 OCT1 polymorphisms were identified in 10 ethnic groups. Significant differences in the frequencies of common alleles were observed among these groups. Met408Val (rs628031) variant was the most extensively explored with metformin responses. Although some genotypes and alleles have been associated with deleterious effects on metformin response, others indeed, exhibited positive effects.Conclusion:Genetic effects of OCT1 polymorphisms on metformin responses were population specific. Further investigations in other populations are required to set ethnicity-specific reference for metformin responses and to obtain a solid basis to design personalized therapeutic approaches for T2DM treatment.

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“…[ 82 ] The importance of pharmacogenetics can be underlined because of the emergence of data such as ~100,000 patients die every year to adverse drug reactions (ADRs) in the US alone, which could be avoided if clinicians have prior knowledge of the patient's genetic profile of drug metabolizing enzymes that determine drug response. [ 84 ] Pharmacogenetic testing involves a careful examination (sequencing) for the presence or absence of specific SNPs and this genetic information can be used in predicting the drug response. To quote Sir William Osler in 1892:…”

Section: Pharmacogenomicsmentioning

confidence: 99%

Genomics era and complex disorders

Rayabarapu

Reddy

2016

Journal of Postgraduate Medicine

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The Human Genome Project (HGP) has identified millions of single nucleotide polymorphisms (SNPs) and their association with several diseases, apart from successfully characterizing the Mendelian/monogenic diseases. However, the dissection of precise etiology of complex genetic disorders still poses a challenge for human geneticists. This review outlines the landmark results of genome-wide association studies (GWAS) with respect to major complex diseases — Coronary artery disease (CAD), type 2 diabetes mellitus (T2DM), and predominant cancers. A brief account on the current Indian scenario is also given. All the relevant publications till mid-2015 were accessed through web databases such as PubMed and Google. Several databases providing genetic information related to these diseases were tabulated and in particular, the list of the most significant SNPs identified through GWAS was made, which may be useful for designing studies in functional validation. Post-GWAS implications and emerging concepts such as epigenomics and pharmacogenomics were also discussed.

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Pharmacogenomics: The Right Drug to the Right Person

Cited by 46 publications

References 7 publications

eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation

eIF3a improve cisplatin sensitivity in ovarian cancer by regulating XPC and p27Kip1 translation

Genetic polymorphisms of organic cation transporter 1 (OCT1) and responses to metformin therapy in individuals with type 2 diabetes

Genomics era and complex disorders

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