Molecular Diagnostics
The future of molecular diagnostics for cancer: a ‘personalised’ perspective
The pharmaceutical industry is still struggling to cure cancer despite pouring enormous resources into the search for new treatments. We take a look at the some of the current technologies for the discovery and delivery of molecular diagnostic, prognostic and predictive tests and speculate on where this area is heading with regard to advanced technologies and likely future requirements.
I
t appears to be general practice now to use the term ‘diagnostic’ to cover three separate cate- gories of test: diagnostic, prognostic and pre- dictive. In so far as these are medical tests provid- ing information about an individual, they can jus- tifiably be considered together. Diagnostic, prog- nostic and predictive tests each contribute some- thing different to our understanding, the sum of the parts helping to build a more complete picture of the patient’s status. To remind ourselves:
l Diagnostic tests seek to reveal something char- acteristic or indicative of a disease. l Prognostic tests provide information as to the likely future course and outcome of a disease. l Predictive tests provide information on the like- ly response of a patient to a drug or therapy.
It is worth mentioning that current FDA practice seems to use the term ‘diagnostic’ generically in relation to testing, to cover all three categories.
Diagnostics
The current paradigm of cancer biology has it that tumours evolve through the accumulation of somatic mutations, which disengage cells from normal behaviour patterns, simultaneously confer-
Drug Discovery World Spring 2011
ring growth advantage. The aim of the diagnostic is therefore to seek out direct or indirect evidence for the presence of that abnormal growth, prefer- ably earlier rather than later in its journey from the benign to the malignant state.
Ideally such evidence should be collected with minimal discomfort (ie, in the least invasive man- ner) to the patient, hence the intense interest in tests that detect proteins or nucleic acids arising from the primary tumour site and found in the blood or in body fluids such as urine. But it is not clear at what stage in the development of a primary solid tumour such biomarkers will become detectable in these fluids. Although a tumour may not yet be invasive and therefore by definition not yet a cancer, once it has grown beyond a critical diameter it is invested with its own, new microvas- culature, into which tumour cell components can be shed. Therefore it is likely that trace amounts of tumour protein and nucleic acids are present in the general circulation even at an early stage in its development. Of course detecting these molecules pre-supposes that they bear some characteristic that differentiates them from those associated with normal cells, and identifying ‘tumour-specific’ pro- teins or other classes of molecule has been the most challenging aspect of the search for circulating or
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By Dr Cliff Murray
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