Precision Medicine
Harnessing the modified proteome
Harnessing the modified proteome for increased diagnostic power

Harnessing the modified proteome for increased diagnostic power

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

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 ’omicsbased 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.

Precision 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 2022 (1). Precision medicine relies on the measurement of specific, objectively-quantifiable biomarkers in patient samples to match treatments and individual 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 providing treatments only to patients who show compatible chemistry for a drug. In this way, non-compatible patients avoid the stress of undergoing unnecessary treatments and any potential toxic side-effects while also saving the high costs associated with such treatments. With costs for Merck’s anti-PD-1 cancer immunotherapy blockbuster, Keytruda (Pembrolizumab), averaging at more 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 insignificant (2,3). Indeed, the high cost of many precision medicines is a barrier 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 treatments (4-6). 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 showing promising trial results or have been licensed for clinical use by the FDA, often demonstrating potent and durable effects in patients. However, due to the targeted nature of these drugs and complex signalling networks at play in the tumour microenvironment, less than half of US patients with cancer were estimated to be eligible for precision medicine drugs in the form of cancer immune checkpoint inhibitors, with a projected response rate of only 12.46% (8).....

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