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Introduction: Precision medicine is an approach that considers genetics, environment and lifestyle factors when prevent and treat diff erent diseases. The important part of precision medicine is pharmacogeneticss, a branch of clinical pharmacology that analyzes how genetic makeup aff ects the response to the drugs. Methods: Since oncology is a fi eld of particular interest in precision medicine, this article summarizes the basic principles of pharmacogenetics testing in cancer treatment. Topic: The following topics have been discussed: Samples for pharmacogenetics testing (peripheral blood, tumor biopsy, liquid biopsy), methods in pharmacogenetics testing (conventional hotspot methods and comprehensive genome profi ling), comprehensive genome profi ling (CGP) in clinical settings and oncology therapy in Serbia that depends on genetic testing. Conclusion: Pharmacogenetics testing provides the delivery of safe and effi cient therapy. The usage of CGP methods opens up the possibility for the usage of therapies directed to genetic markers across tumor types. However, this approach needs evaluation through well-designed research projects and clinical trials. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases are the leading cause of morbidity and mortality worldwide. Despite considerable advances in cardiovascular pharmacology, significant inter-individual variability in response to drugs affects both their efficacy and safety profile. Drug-gene associations have emerged as important factors determining a spectrum of response to therapy. Pharmacogenomic interactions in cardiovascular medicine are also involved in etiology of adverse effects that may be life-threatening, such as statininduced myopathy or a hemorrhage/thrombosis event during anticoagulant therapy. Introduction of genetic tests prior to the initiation of therapy and implementation of genetically-guided therapy represent a step forward to achieving a goal of individualized medicine in cardiology, already present in recommendations for warfarin and clopidogrel. However, further investigations addressing genomic predictors of variability in response to drugs are still needed and translating these findings into routine clinical practice remains a substantial challenge. [ABSTRACT FROM AUTHOR]

Methotrexate (MTX) is one of the essential medicines used in the treatment of rheumatoid arthritis (RA). The efficacy of treatment of rheumatoid arthritis with MTX is between 46 % and 65 % (as assessed by ACR 20). Pharmacogenetics deals with genetic predisposition of the patient to respond to the treatment. The aim of the study was to determine whether single nucleotide polymorphism (SNP) C677T (rs1801133) of the MTHFR gene are predictive of peroral MTX efficacy or are associated with lower change of DAS28 (ΔDAS 28) after a 6-month MTX treatment in RA adult patient cohort of the East Bohemian population. The 120 patients were enrolled in the study, all of whom fulfilled the American College of Rheumatology (ACR) 1987 RA criteria, and currently or previously taking MTX oral treatment, either as a monotherapy (n = 65) or in a combination with DMARDs (n = 55). Genotyping was performed using qPCR allelic discrimination. We did not found any association of C677T SNP on MTX treatment inefficacy in dominant model CC versus (CT+TT). However, when ΔDAS 28 was used as a measure of MTX treatment efficacy, MTHFR 677CT genotype was significantly associates with less favourable response to MTX (P = 0.01) in case of MTX monotherapy. Our data thus shows that C677T SNP might be associated with theless favourable response to low dose MTX treatment. [ABSTRACT FROM AUTHOR]

Colorectal cancer is a relatively common tumor with incidence that has been increasing during recent decades. Despite the rapid advances in treatment of colorectal cancer, the best way to combine and sequence all available drugs to optimize treatment is not yet established. The majority of cytotoxic drugs used in therapy of colorectal cancer have a dose related effect and narrow therapeutic index. Hence, dosing of cytotoxic drugs is considered very important. Current modalities for therapy and dose selection give restricted possibilities to equalise inter-individual variations which are dependent on physiological, genetic and environmental factors. In this article, an overview of current possibilities of personalized medicine in therapy of colorectal cancer is presented. This includes review of the most important gene polymorphisms important for safety and efficacy of cytotoxic therapy in colorectal cancer, and evaluation of their importance for the current clinical practice. Despite raising knowledge, providing individual treatment with low toxicity and significant benefits is still an unsolved problem. Reasons for this are the lack of knowledge on distribution of these polymorphisms in the population, importance of non-genetic factors, price of genetic testing and still limited data from controlled clinical trials confirming the clinical usefulness of pharmacogenetic testing. Although the initial costs of cancer management and personalized medicine may be high, in the future they may result in significant benefits from both a clinical and economical perspective. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a heterogeneous group of disorders in which particular disease phenotypes can be characterized by a specific etiology and/or pathogenesis of the disease, but in many cases its classification is greatly impeded due to significant phenotype overlapping. Diabetes is a wordwide epidemic with significant health and economic consequences. The frequency of type 2 diabetes (T2D) is much higher than type 1 diabetes (T1D). In adults, around 285 million people suffer from T2DM with a projected rise to 438 million in the next 20 years. A variety of pharmacological treatments exist for patients with T2D, in addition to dietary and physical activity. Pharmacologically, diabetes is treated with nine major classes of approved drugs, including insulin and its analogues, sulfonylureas, biguanides, thiazo-lidinediones (TZDs), meglitinides, a-glucosidase inhibitors, amylin analogues, incretin hormone mimetics, and dipep-tidyl peptidase 4 (DPP4) inhibitors. Treatment strategy for T2D is based mostly on oral hypoglycemic drug (OHD) efficacy assessed usually by HbA1c and/or fasting plasma glucose. The patients are often treated with more than one OHD in combination with the purpose to receive more effective treatment. Characterization of drug response is expected to substantially increase the ability to provide patients with the most effective treatment strategy. If pharmacogenetic testing for diabetes drugs could be used to predict treatment outcome, appropriate measures could be taken to treat T2D more efficiently. To date, major pharmacogenetic studies have focused on response to sulfonylureas, biguanides, and TZDs, the most used OHD. A comprehensive review of the pharmacogenetic studies of specific OHD is presented in this article. Understanding the pharmacogenetics of these drugs will provide critical baseline information for the development and implementation of a genetic screening program into therapeutic decision making, enabling a personalized medicine approach for T2D patients. [ABSTRACT FROM AUTHOR]