Treatment and understanding of BCR::ABL1-positive leukaemias is a precision medicine success story. Our appreciation of the BCR::ABL1 gene and resulting BCR::ABL1 oncoprotein in chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive (Ph+) acute leukaemias, has led to treatment advances associated with exceptional improvements in patient outcomes with normal life expectancy for many patients with chronic phase (CP-)CML. However, despite these major therapeutic advances, the management of Ph+ leukaemias remains complex, with development of specific resistance mutations on treatment, as well as the need for lifelong therapy in most patients due to the persistence of CML stem cells despite prolonged tyrosine kinase inhibitors (TKIs) treatment. BCR::ABL1-specific TKIs are associated with chronic toxicities affecting quality-of-life in many patients but can also result in more serious pulmonary and cardiovascular complications. Dose optimisation is increasingly being used to manage side effects and maintain molecular response in CML patients. Here, we review the development of BCR::ABL1-specific TKIs from the discovery of imatinib in 1996 to the more recent second- and third-generation TKIs and emerging specifically targeting the ABL myristoyl pocket (STAMP) inhibitors. We will also evaluate the current evidence for treatment of BCR::ABL1-positive leukaemias, including TKI discontinuation in optimally responding CP-CML patients.

Clustered regularly interspaced short palindromic repeats and other genome editing technologies have the potential to transform the lives of people affected by genetic disorders for the better. However, it is widely recognised that they also raise large ethical and policy questions. The focus of this article is on how national genome editing policy might be developed in ways that give proper recognition to these big questions. The article first considers some of the regulatory challenges involved in dealing these big ethical and social questions, and also economic issues. It then reviews the outcomes of a series of major reports on genome editing from international expert bodies, with a particular focus on the work of the World Health Organization’s expert committee on genome editing. The article then summarises five policy themes that have emerged from this review of the international reports together with a review of other literature, and the authors’ engagement with members of the Australian public and with a wide range of experts across multiple disciplines. Each theme is accompanied by one to three pointers for policymakers to consider in developing genome editing policy.

Diabetes mellitus is prevalent worldwide and affects 1 in 10 adults. Despite the successful development of glucose-lowering drugs, such as glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter-2 inhibitors recently, the proportion of patients achieving satisfactory glucose control has not risen as expected. The heterogeneity of diabetes determines that a one-size-fits-all strategy is not suitable for people with diabetes. Diabetes is undoubtedly more heterogeneous than the conventional subclassification, such as type 1, type 2, monogenic and gestational diabetes. The recent progress in genetics and epigenetics of diabetes has gradually unveiled the mechanisms underlying the heterogeneity of diabetes, and cluster analysis has shown promising results in the substratification of type 2 diabetes, which accounts for 95% of diabetic patients. More recently, the rapid development of sophisticated glucose monitoring and artificial intelligence technologies further enabled comprehensive consideration of the complex individual genetic and clinical information and might ultimately realize a precision diagnosis and treatment in diabetics.

Precision Medicine is an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle. Autoimmune diseases are those in which the body’s natural defense system loses discriminating power between its own cells and foreign cells, causing the body to mistakenly attack healthy tissues. These conditions are very heterogeneous in their presentation and therefore difficult to diagnose and treat. Achieving precision medicine in autoimmune diseases has been challenging due to the complex etiologies of these conditions, involving an interplay between genetic, epigenetic, and environmental factors. However, recent technological and computational advances in molecular profiling have helped identify patient subtypes and molecular pathways which can be used to improve diagnostics and therapeutics. This review discusses the current understanding of the disease mechanisms, heterogeneity, and pathogenic autoantigens in autoimmune diseases gained from genomic and transcriptomic studies and highlights how these findings can be applied to better understand disease heterogeneity in the context of disease diagnostics and therapeutics.

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.

The aim of liquid biopsies is to obtain tumor information via the molecular interrogation of liquid samples, including blood and urine. As a minimally invasive procedure, liquid biopsies have attracted attention. A series of studies have reported associations of biomarkers such as circulating tumor DNA, cell-free DNA and extracellular vesicles with urological cancers, especially prostate cancer (PCa), and demonstrated the promising potential of liquid biopsies. In this review, we summarize recent clinical translational studies of liquid biopsies in PCa and other urological cancers, including bladder cancer and renal cell carcinoma. The number of translational studies was limited, and most of the studies focused on PCa. Biomarkers isolated from blood by different detection methods could be applied in clinical practice to predict prognosis and treatment response in advanced PCa. The other applications in urological cancers identified in previous studies remain to be explored further. Current studies are limited due to the lack of ideal standard detection methods for biomarkers. In the future, with advances in methodology, more translational studies will be conducted to identify potential applications of liquid biopsies in urological cancers.

Precision medicine for cardiomyopathies holds great promise to improve patient outcomes costs by shifting the focus to patient-specific treatment decisions, maximising the use of therapies most likely to lead to benefit and minimising unnecessary intervention. Dilated cardiomyopathy (DCM), characterised by left ventricular dilatation and impairment, is a major cause of heart failure globally. Advances in genomic medicine have increased our understanding of the genetic architecture of DCM. Understanding the functional implications of genetic variation to reveal genotype-specific disease mechanisms is the subject of intense investigation, with advanced cardiac imaging and mutliomics approaches playing important roles. This may lead to increasing use of novel, targeted therapy. Individualised treatment and risk stratification is however made more complex by the modifying effects of common genetic variation and acquired environmental factors that help explain the variable expressivity of rare genetic variants and gene elusive disease. The next frontier must be expanding work into early disease to understand the mechanisms that drive disease expression, so that the focus can be placed on disease prevention rather than management of later symptomatic disease. Overcoming these challenges holds the key to enabling a paradigm shift in care from the management of symptomatic heart failure to prevention of disease.