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Oxford’s genetic expertise is centred around using genetic information to better understand phenotypic and mechanistic aspects of disease, as well as integrating the use of genetic information in the detection, diagnosis and treatment of cancer. Applying this to the challenges of cancer takes many forms, such as identifying novel pathways that contribute to tumour behaviour, how germline mutations can affect an individual’s risk of cancer, and how a tumour’s genetics influence how it responds to treatment.

Epigenetic changes in cells is one of the hallmarks of cancer. Small units such as RNA can modify and control gene expression in a way that is only now being understood in relation to human health. Oxford research strives to understand how epigenetic information in a cell is stored in the form of chemical modifications within its DNA, RNA and histone proteins, as well as how modifications can ultimately impact biological processes and lead to cancer. With this information, novel single-cell technologies and chemical biology can be applied to the development of new treatments in a way that targets epigenetic mechanisms.

As the vehicle for inherited information, maintaining the quality of the information stored in the genome is a key activity undertaken by the cells of all organisms. This requires maintaining both the genetic sequence and number of chromosomes. Understanding how cells reproduce an exact replica of their genome, and repair damage when it occurs, continues to be a focus of researchers across Oxford. There is a diverse array of errors that can occur during the process of replication, as well as in response to environmental factors such as chemicals and radiation. Subsequently, the ways in which cells detect and repair them are equally varied. Mechanistic insights into these pathways are key to understanding how their defects contribute to tumour development and a patient’s response to different types of therapy.

Differences in metabolic processes in normal and cancer cells (e.g. hypoxia – low oxygen) present opportunities for targeted therapies, but can also interfere with standard treatments such as radiotherapy. These metabolic differences are driven by local, genetic and environmental factors and other co-morbidities such as obesity. It is therefore important to understand hypoxia, signalling, nucleotide metabolism, obesity and drug associated changes to metabolism and how they affect cell behaviour.

Exosomes (a type of extracellular vesicle that originates from cells and circulates in the blood) contain multiple types of proteins and RNA fragments that provide a fingerprint of the cells of origin. They are also involved in cell-to-cell communication and can be hijacked by cancer cells to evade the immune response, manipulate the tumour microenvironment and facilitate metastasis to other areas. Oxford researchers are applying their unique understanding of exosomes to better treat cancer, and utilise their potential to detect tumours.

The differentiation of stem cells into the various cell types is critical to the development and maintenance of healthy tissues. Oxford is home to researchers studying how the fate of cells is controlled for tissue homeostasis, and how its dysfunction drives disease. Cancer researchers are seeking to understand the molecular mechanisms that regulate the formation of cancer stem cells (CSCs), and their contribution to tumour behaviour. Like normal stem cells, CSCs are able to self-renew and produce differentiated progeny. Unlike normal stem cells, they do this in an uncontrolled way that results in the formation of malfunctioning tissues and organs. Understanding how normal stem cells function will be key to understanding how CSCs give rise to tumours, metastases, and why they are resistant to therapies.

Early-Stage Cancer Biology provides a fundamental understanding of how cancer begins and develops. Many studies aim to identify the differences between cellular processes in healthy vs. cancer cells. However, the development of cancer is dynamic and the study of these processes over time (or through intermediate states) is required to capture the earliest indicators of cancer, which could be hard to spot while only investigating established or late-stage tumours. This approach taken by Oxford researchers will enable a new window of opportunity for early detection.

The behaviour of tissues can be influenced by a range of features that includes those listed above, as well as surrounding stromal cells, immune cells, matrix components, the acid-base microenvironment, and hypoxia. Oxford research seeks to study the cross-talk between these, their relationship to cell function and how these change over space and time, to build a complete understanding of tissue behaviour in health and disease.