The host immune system status remains an unresolved mystery among several malignancies. An immune-compromised state or smart immune-surveillance tactics orchestrated by cancer cells are the primary cause of cancer invasion and metastasis. Taking a closer look at the tumour-immune microenvironment, a complex network and crosstalk between infiltrating immune cells and cancer cells mediated by cytokines, chemokines, exosomal mediators and shed ligands are present. Cytokines such as interleukins can influence all components of the tumour microenvironment (TME), consequently promoting or suppressing tumour invasion based on their secreting source. Interleukin-10 (IL-10) is an interlocked cytokine that has been associated with several types of malignancies and proved to have paradoxical effects. IL-10 has multiple functions on cellular and non-cellular components within the TME. In this review, the authors shed the light on the regulatory role of IL-10 in the TME of several malignant contexts. Moreover, detailed epigenomic and pharmacogenomic approaches for the regulation of IL-10 were presented and discussed.

Psychotropic medication efficacy and tolerability are critical treatment issues faced by individuals with psychiatric disorders and their healthcare providers. For some people, it can take months to years of a trial-and-error process to identify a medication with the ideal efficacy and tolerability profile. Current strategies (e.g. clinical practice guidelines, treatment algorithms) for addressing this issue can be useful at the population level, but often fall short at the individual level. This is, in part, attributed to interindividual variation in genes that are involved in pharmacokinetic (i.e. absorption, distribution, metabolism, elimination) and pharmacodynamic (e.g. receptors, signaling pathways) processes that in large part, determine whether a medication will be efficacious or tolerable. A precision prescribing strategy know as pharmacogenomics (PGx) assesses these genomic variations, and uses it to inform selection and dosing of certain psychotropic medications. In this review, we describe the path that led to the emergence of PGx in psychiatry, the current evidence base and implementation status of PGx in the psychiatric clinic, and finally, the future growth potential of precision psychiatry via the convergence of the PGx-guided strategy with emerging technologies and approaches (i.e. pharmacoepigenomics, pharmacomicrobiomics, pharmacotranscriptomics, pharmacoproteomics, pharmacometabolomics) to personalize treatment of psychiatric disorders.

Humans operating in extreme environments often conduct their operations at the edges of the limits of human performance. Sometimes, they are required to push these limits to previously unattained levels. As a result, their margins for error in execution are much smaller than that found in the general public. These same small margins for error that impact execution may also impact risk, safety, health, and even survival. Thus, humans operating in extreme environments have a need for greater refinement in their preparation, training, fitness, and medical care. Precision medicine (PM) is uniquely suited to address the needs of those engaged in these extreme operations because of its depth of molecular analysis, derived precision countermeasures, and ability to match each individual (and his or her specific molecular phenotype) with any given operating context (environment). Herein, we present an overview of a systems approach to PM in extreme environments, which affords clinicians one method to contextualize the inputs, processes, and outputs that can form the basis of a formal practice. For the sake of brevity, this overview is focused on molecular dynamics, while providing only a brief introduction to the also important physiologic and behavioral phenotypes in PM. Moreover, rather than a full review, it highlights important concepts, while using only selected citations to illustrate those concepts. It further explores, by demonstration, the basic principles of using functionally characterized molecular networks to guide the practical application of PM in extreme environments. At its core, PM in extreme environments is about attention to incremental gains and losses in molecular network efficiency that can scale to produce notable changes in health and performance. The aim of this overview is to provide a conceptual overview of one approach to PM in extreme environments, coupled with a selected suite of practical considerations for molecular profiling and countermeasures.

Precision medicine envisages the integration of an individual’s clinical and biological features obtained from laboratory tests, imaging, high-throughput omics and health records, to drive a personalised approach to diagnosis and treatment with a higher chance of success. As only up to half of patients respond to medication prescribed following the current one-size-fits-all treatment strategy, the need for a more personalised approach is evident. One of the routes to transforming healthcare through precision medicine is pharmacogenomics (PGx). Around 95% of the population is estimated to carry one or more actionable pharmacogenetic variants and over 75% of adults over 50 years old are on a prescription with a known PGx association. Whilst there are compelling examples of pharmacogenomic implementation in clinical practice, the case for cardiovascular PGx is still evolving. In this review, we shall summarise the current status of PGx in cardiovascular diseases and look at the key enablers and barriers to PGx implementation in clinical practice.

Pharmacogenetics, the study of how interindividual genetic differences affect drug response, does not explain all observed heritable variance in drug response. Epigenetic mechanisms, such as DNA methylation, and histone acetylation may account for some of the unexplained variances. Epigenetic mechanisms modulate gene expression and can be suitable drug targets and can impact the action of nonepigenetic drugs. Pharmacoepigenetics is the field that studies the relationship between epigenetic variability and drug response. Much of this research focuses on compounds targeting epigenetic mechanisms, called epigenetic drugs, which are used to treat cancers, immune disorders, and other diseases. Several studies also suggest an epigenetic role in classical drug response; however, we know little about this area. The amount of information correlating epigenetic biomarkers to molecular datasets has recently expanded due to technological advances, and novel computational approaches have emerged to better identify and predict epigenetic interactions. We propose that the relationship between epigenetics and classical drug response may be examined using data already available by (1) finding regions of epigenetic variance, (2) pinpointing key epigenetic biomarkers within these regions, and (3) mapping these biomarkers to a drug-response phenotype. This approach expands on existing knowledge to generate putative pharmacoepigenetic relationships, which can be tested experimentally. Epigenetic modifications are involved in disease and drug response. Therefore, understanding how epigenetic drivers impact the response to classical drugs is important for improving drug design and administration to better treat disease.

Precision Medicine is an approach to disease treatment and prevention taking into account individual genetic, environmental, therapeutic and lifestyle variability for each person. This holistic approach to therapeutics is intended to enhance drug efficacy and safety not only across healthcare systems but for individual patients. While weight and to some extent gestational age have been considered in determining drug dosing in children, historically other factors including genetic variability have not been factored into therapeutic decision making. As our knowledge of the role of ontogeny and genetics in determining drug efficacy and safety has expanded, these insights have provided new opportunities to apply principles of Precision Medicine to the care of infants, children and youth. These opportunities are most likely to be achieved first in select sub-groups of children. While there are many challenges to the successful implementation of Precision Medicine in children including the need to ensure that Precision Medicine enhances rather than reduces equity in children’s health care rather, there are many more opportunities. Research, advocacy, planning and teamwork are required to move Precision Medicine forward in children in pursuit of the common goal of safe and effective drug therapy.

While first gene-drug pairs have emerged to be clinically actionable in the treatment of major depressive disorders (MDD) (e.g., CYP2D6 and TCAs/SSRIs), genomic studies have not yet been successful in identifying replicable and valid biomarkers of pharmacological treatment outcome. While some trials suggest that candidates such as CYP2D6, CYP2C19, CYP1A2, SLC6A4 and HTR2A polymorphisms may improve the prediction of response/remission, these results should be interpreted cautiously and required confirmation in larger samples. This presentation will cover state of the art of pharmacogenomics for MDD as well as the emerging field of pharmacotranscriptomics and functional genomics analyses in MDD. Specifically, pharmacotranscriptomics in combination with genomics may be a promising avenue in overcoming some of the current limitations in treatment response prediction research. More recently, the combined genetic effect of polygenic risk scores has shown promising results in predicting treatment response. Importantly, adequately large and well phenotyped clinical trials are required to be conducted with pharmacogenomics/-transcriptomics prospectively in mind.

Pharmacogenetic influences on therapeutic response to e.g. antidepressant or neuroleptic treatment are poorly understood and the lack of efficacy in many of the patients together with side effects can both limit therapy and compliance. Thus the aim of pharmacogenetics and pharmacogenomics is to provide predictive tools for the response to psychopharmacologic agents in the therapy of psychiatric disorders and in that ways to provide a real personalized psychiatry. The following review will summarize the current stage of pharmacogenetics and pharmacogenomics and will critically discuss the possibilities of a personalized medicine.

Objectives: Companion diagnostic tests (CDx) are used to measure an individual's protein or gene expression (biomarkers) to inform choice of therapy. The increasing number of drugs requiring CDx poses challenges for regulatory and reimbursement policies. To better understand this issue, an environmental scan was conducted by the Canadian Agency for Drugs and Technologies in Health (CADTH).

Methods: The environmental scan was based on a focused literature search and feedback solicited from targeted stakeholders.

Results: The global market for CDx is expected to grow considerably until the end of this decade, with compound annual growth rate around 20 percent. Several factors may impact the adoption of CDx, including the potential cost-savings associated with reduced treatment failures and adverse reactions. Anticipating an expansion in drugs with CDx, some countries have updated their regulatory frameworks, including the United States where the FDA released new guidance in 2014. With respect to reimbursement, both the United Kingdom and Australia updated their evaluation frameworks to inform reimbursement decisions; however, several countries, including Canada, have not published policies for co-dependent technology.

Conclusion: The market size for CDx is expected to considerably expand in the future. The drive in uptake may be influenced by many factors including an increased knowledge of biomarkers and molecular drivers of disease and the potential cost-savings associated with fewer treatment failures and adverse reactions. Assessing whether such benefits materialize is important. Health technology assessment will play an important role in informing policies regarding the clinical use and funding of pharmaceuticals with CDx.

Pharmacogenomics has the potential of transforming clinical research and improving healthcare in sub-Saharan Africa (SSA). The role of African genome diversity and the opportunities for pharmacogenomics research are highlighted and will enable discovery of novel genetic mechanisms and validation of established markers. African genomics and biobank consortia will play an important role in building capacity for pharmacogenomics in SSA.

Older people are high consumers of prescription drugs and are at increasing risk of polypharmacy and adverse reactions. Pharmacokinetic and pharmacodynamic modifications due to age and co-morbidities are an important consideration, but pharmacological background evidence to guide safe and effective therapeutic approaches are often inadequate since the older population is under-represented in clinical trials. We review the pharmacokinetic and pharmacodynamic changes that are characteristic in old age and consider evidence regarding potentially safer prescription and monitoring of drugs commonly used in older patients. We also introduce the possible role of pharmacogenomics and therapeutic drug monitoring as tools to guide the individualization of drug therapy.

Personalised medicine has finally been featured in psychiatric journals, but psychiatrists have mainly focused on the promise of using disease mechanisms to personalise treatment. Psychiatric disorders such as schizophrenia and depression are not diseases, in the medical sense, and are probably more like syndromes. Instead of spending much time and effort focusing on the mechanisms of diseases that may instead be syndromes, the author believes that psychiatrists should (1) learn more about personalising prescription via drug mechanisms, a pharmacological approach to personalised medicine; and (2) reconsider prior attempts by traditional clinical psychopharmacologists to use sophisticated clinical approaches that try to subdivide psychiatric syndromes into groups that may be more homogenous for treatment response.

Cardiovascular diseases are the leading cause of death worldwide. Essential hypertension is a major risk factor for the development of other cardiovascular diseases and is caused by a combination of environmental and genetic factors, with up to 50% of blood pressure variance currently attributed to an individual's genetic makeup. By studying genes that cause monogenic forms of hypertension and pathways relevant to blood pressure control, a number of polymorphisms have been identified that increase an individual's risk of developing high blood pressure. We report on candidate gene association studies and genome-wide association studies that have been performed to date in the field of hypertension research. It is becoming clear that for the majority of people there is no single gene polymorphism that causes hypertension, but rather a number of common genetic variants, each having a small effect. Using pharmacogenomics to personalize the treatment of hypertension holds promise for achieving and sustaining normotensive pressures quickly, while minimizing the risk of adverse reactions and unwanted side-effects. This will decrease the risk of stroke and myocardial infarction in individuals and lead to a reduced burden of disease upon society as a whole.