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Precision Medicine


Harnessing the modified proteome for increased diagnostic power


Relevant biomarkers are vitally important in personalised medicine, guiding patient matching to specific therapies for earlier, easier and more effective disease identification and treatment. Here we trace the expectations of ’omics- based healthcare interventions, from the increased understanding stemming from genomic and transcriptomic revolutions, through the lack of validated proteomic biomarkers, to the developing recognition of the potential of the modified proteome. Examining traditional methods and new advances in the field of proteomics that allow such investigations, we will discuss how they are currently being employed, with the potential to improve patient outcomes and reduce healthcare costs.


P


recision medicine holds the potential for the treatment for many diseases that have proven unresponsive to traditional therapies, such as


cancer and autoimmune conditions. This strategy has seen much promise, with the field of precision medicine predicted to increase from a global value of $38.92 billion in 2015 to $88.64 billion by 20221. Precision medicine relies on the measure- ment of specific, objectively-quantifiable biomark- ers in patient samples to match treatments and indi- vidual patients according to their specific genetics or biochemistry. For each specific disease these biomarkers may be predictive, prognostic or both. The aim of precision medicine is to improve the


benefit-to-risk profile of many therapeutics by pro- viding treatments only to patients who show com- patible chemistry for a drug. In this way, non-com- patible patients avoid the stress of undergoing unnecessary treatments and any potential toxic side-effects while also saving the high costs associ- ated with such treatments. With costs for Merck’s anti-PD-1 cancer immunotherapy blockbuster, Keytruda (Pembrolizumab), averaging at more


Drug Discovery World Winter 2019/20


than $100,000 per patient, and Novartis’ CAR-T drug for leukaemia, Kymriah (Tisagenlecleucel), costing more than $350,000 per treatment, these cost savings are far from insignificant2,3. Indeed, the high cost of many precision medicines is a bar- rier to uptake for patients, healthcare services and payers across the globe. Gleevec (Imatinib), a tyrosine kinase inhibitor


manufactured by Novartis, is one example of a precision medicine therapeutic success story. Used in the treatment of chronic myeloid leukaemia, patients receiving Gleevec as a first-line treatment showed an overall 10-year survival rate of 83.3% compared to the 43-65% 10-year survival rate observed with previous treatments4-6. Herceptin (Trastuzumab) offers another milestone in the treatment of early and metastatic HER2 positive breast cancer, with 10-year survival rates showing improvement from 75.2% with chemotherapy alone to 84% with the use of Herceptin. Rates of survival without recurrence have also increased in response to Herceptin treatment from 62.2% to 73.7%7. Many other precision medicine drugs are


33


By Dr David Bramwell, Dr Steven Laval and Dr Jane McLeod


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