Precision oncology is a rapidly evolving concept that holds great promise in cancer treatment. However, a cancer complexity attributed to genomic and acquired tumour heterogeneity limits treatment effectiveness and increases toxicity. These limitations refer to both systemic therapies and radiotherapy, which are two mainstays of non-invasive cancer treatment. By understanding cancer heterogeneity and utilising advanced tools to personalise treatment strategies, precision oncology has the potential to revolutionise cancer care. In this article, we review the current status of precision oncology in solid tumours, specifically focusing on the impact of tumour heterogeneity and genomic patient features on systemic therapies and radiation. We also discuss the implementation of novel tools, such as next-generation sequencing and liquid biopsies, to overcome this problem.

The interplay between genetic and environmental factors plays a significant role in interindividual variation in immune and inflammatory responses. The availability of high-throughput low-cost genotyping and next-generation sequencing has revolutionized our ability to identify human genetic variation and understand how this varies within and between populations, and the relationship with disease. In this review, we explore the potential of genomics for patient benefit, specifically in the diagnosis, prognosis and treatment of inflammatory and immune-related diseases. We summarize the knowledge arising from genetic and functional genomic approaches, and the opportunity for personalized medicine. The review covers applications in infectious diseases, rare immunodeficiencies and autoimmune diseases, illustrating advances in diagnosis and understanding risk including use of polygenic risk scores. We further explore the application for patient stratification and drug target prioritization. The review highlights a key challenge to the field arising from the lack of sufficient representation of genetically diverse populations in genomic studies. This currently limits the clinical utility of genetic-based diagnostic and risk-based applications in non-Caucasian populations. We highlight current genome projects, initiatives and biobanks from diverse populations and how this is being used to improve healthcare globally by improving our understanding of genetic susceptibility to diseases and regional pathogens such as malaria and tuberculosis. Future directions and opportunities for personalized medicine and wider application of genomics in health care are described, for the benefit of individual patients and populations worldwide.

The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the ‘molecular tumour board’ into ‘standard of care’ ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.

Recent advances in genetic and epigenetic research have underscored the significance of 5-hydroxymethylcytosine (5hmC) in neurodevelopmental disorders (NDDs), such as autism spectrum disorder (ASD) and intellectual disability (ID), revealing its potential as both a biomarker for early detection and a target for novel therapeutic strategies. This review article provides a comprehensive analysis of the role of 5hmC in NDDs by examining both animal models and human studies. By examining mouse models, studies have demonstrated that prenatal environmental challenges, such as maternal infection and food allergies, lead to significant epigenetic alterations in 5hmC levels, which were associated with NDDs in offspring, impacting social behavior, cognitive abilities and increasing ASD-like symptoms. In human studies, researchers have linked alterations in 5hmC levels NDDs through studies in individuals with ASD, fragile X syndrome, TET3 deficiency and ID, specifically identifying significant epigenetic modifications in genes such as GAD1, RELN, FMR1 and EN-2, suggesting that dysregulation of 5hmC played a critical role in the pathogenesis of these disorders and highlighted the potential for targeted therapeutic interventions. Moreover, we explore the implications of these findings for the development of epigenetic therapies aimed at modulating 5hmC levels. The review concludes with a discussion on future directions for research in this field, such as machine learning, emphasizing the need for further studies to elucidate the complex mechanisms underlying NDDs and to translate these findings into clinical practice. This paper not only advances our understanding of the epigenetic landscape of NDDs but also opens up new avenues for diagnosis and treatment, offering hope for individuals affected by these conditions.

Artificial intelligence (AI) holds immense promise for accelerating and improving all aspects of drug discovery, not least target discovery and validation. By integrating a diverse range of biological data modalities, AI enables the accurate prediction of drug target properties, ultimately illuminating biological mechanisms of disease and guiding drug discovery strategies. Despite the indisputable potential of AI in drug target discovery, there are many challenges and obstacles yet to be overcome, including dealing with data biases, model interpretability and generalisability, and the validation of predicted drug targets, to name a few. By exploring recent advancements in AI, this review showcases current applications of AI for drug target discovery and offers perspectives on the future of AI for the discovery and validation of drug targets, paving the way for the generation of novel and safer pharmaceuticals.