Precision Medicine

refine and optimise DIGE approaches for biomark- er identification and assay of proteomic signatures offers the required precision to bring proteomic and PTM biomarkers to the clinic for precision medicine. Precision medicine has delivered effective thera-

peutics and much hope for some patients, yet the identification of actionable molecular targets to pinpoint future therapies is essential to this field. Analysing modified proteins as signatures of dis- ease offers a range of largely unexplored potential biomarkers and is beginning to show promise in this field. It is well documented that glycans on the cell surface are fundamentally altered in tumour cells and that these changes happen early in the development of cancers, making them powerful early diagnostic markers. The specific changes in tumour cell glycosylation patterns determine the immune-inhibitory properties of the tumour, often allowing tumour cells to evade immune detection and prevent the arousal of an anti-tumour response. Strategies that prevent the interaction of tumour-associated glycans with inhibitory immune receptors could, therefore, serve as novel immune checkpoint inhibition therapies36. Recent research has shown that modification of tumour cell glyco- sylation patterns, through metabolic mimetics or glycosylation enzymes conjugated to tumour-tar- geting enzymes, reduced tumour growth and acti- vated T-cell mediated anti-tumour responses43,44. The importance of considering patient PTM pro- files was further highlighted in the trials of the vac- cine Biomira (Theratope) which targeted anti- tumour associated glycan for the treatment of metastatic breast cancer22,23. During Phase II tri- als, a significant increase in patient survival was observed23. However, Phase III trials failed to reproduce these findings, probably owing to het- erogeneity in the expression of the tumour PTM profile, which was not evaluated prior to patient selection26,36. Delivering biomarkers for accurate disease diag-

nosis and treatment is essential to precision medicine. While omics-based approaches have pro- duced many effective biomarkers, particularly within the field of genomics, the proteomics field is not currently as advanced in translating findings to the clinic. A large part of this may be due to the requirement for refinement of proteomic profiling methods to identify and quantify clinical biomark- ers and the vast complexity of the proteome in comparison to more static biological library of the genome. Understanding and being able to accu- rately analyse PTMs is an important challenge within this area that once we begin to meet, via


improved MS protocols or alternative techniques such as DIGE, could begin to deliver actionable clinical biomarkers for improved precision medicine across the spectrum of disease. DDW

With a PhD and research background in human visual perception and neural imaging, Dr David Bramwell established a career developing software solutions for proteomic analyses with Nonlinear Dynamics. His current role is as the Chief Technical Officer for Biosignatures, a company focused on the development of novel large-scale proteomics and AI-based diagnostic solutions for clinical application.

Following a DPhil at the University of Oxford and subsequent postdoctoral work at Newcastle University, Dr Steven Laval is currently Principal Scientist at Biosignatures, developing the proteom- ic platform and machine learning software solu- tions for diagnostic and clinical application.

Dr Jane McLeod completed her PhD at the University of York and postdoctoral research at the University of Sheffield in protein engineering. Since then she has worked as a science writer across academia and industry.

Drug Discovery World Winter 2019/20

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