Elsevier

Drug Discovery Today

Volume 15, Issues 3–4, February 2010, Pages 115-120
Drug Discovery Today

Review
Post Screen
Progress towards personalized medicine

https://doi.org/10.1016/j.drudis.2009.11.001Get rights and content

Personalized medicine is the tailoring of therapies to defined subsets of patients based on their likelihood to respond to therapy or their risk of adverse events. The advent of improved genomic tools has greatly hastened our understanding of the molecular pathology of diseases, enabling us to redefine disease at the molecular level. The development of molecularly targeted therapies, coupled with improved diagnostic criteria, holds the promise of delivering a new paradigm in drug development. But how far have we come, and how close is personalized medicine to delivering on its promise?

Section snippets

What is personalized medicine?

It is ten years since the term ‘personalized medicine’ was first used in the context that we understand today [7], and the intervening years have seen a dramatic expansion in its prevalence in the scientific community [8] and a widening recognition in the wider population. There is no single universally accepted definition of personalized medicine, but most definitions align with the phrase ‘the right drug for the right patient’. It is hard for even the most cynical opponent of personalized

Targeted therapy in cancer – setting the example

The treatment response rates in cancer are amongst the lowest for any major disease, and this, coupled with the now well-established genomic basis of cancer pathology, has long put cancer research in the vanguard of personalized medicine. Oncology has delivered key successes in personalized medicine: the examples provided by Herceptin in breast cancer and Gleevec in chronic myeloid leukaemia (CML) have long carried the mantle for individualized therapy. A humanized monoclonal antibody directed

Molecular diagnostics – prognosis and prediction

Pathologically defined disease subsets described by the location of the tumour or the originating cell have been fundamental for medical treatment in cancer for decades. Oestrogen and progesterone receptor status in breast cancer has long been known to predict response to endocrine therapies such as tamoxifen and arguably represent one of the first examples of personalized medicine [18]. The clear molecular differences seen in breast cancer have also lent themselves to genomic profiling, and

Targeted therapy in cancer – keep the pathway intact

Despite the early successes of Herceptin and Gleevec, there was little encouragement for personalized medicine advocates in the area of targeted therapies for many years. Indeed, the failure of key drugs such as AstraZeneca's Iressa (Gefitinib) undermined the rationale. Iressa, an inhibitor of the epidermal growth factor (EGFR) receptor tyrosine kinase that was approved by the FDA in 2003 based on phase II data in non-small cell lung carcinoma (NSCLC), seemed to hold promise for personalized

Companion diagnostics – where next?

As well as heralding the era of personalized medicine, Herceptin can also take the credit for heralding the advent of companion diagnostics. Approved along with a diagnostic test for HER-2 expression monitoring and a strategy for defining expression levels for inclusion or exclusion of patients from therapy, the Hercept test set the precedent for other companion diagnostics to follow. Clearly, accurately defining the patients likely to respond to a therapy is as crucially important as the

Beyond oncology

Examples of therapy targeted at specific disease subpopulations have been slow to develop outside of oncology, but they are beginning to appear [38]. Selentry (maraviroc) is the first licensed CCR5 co-receptor antagonist drug that blocks HIV viral uptake into CD4 T cells [39] and represents the clearest example of targeted therapy outside oncology. To gain entry into T cells, the HIV virus interacts with both the CD4 receptor and either CCR5 or CXCR4 co-receptors. Selentry binds to CCR5, thus

Concluding remarks

After a slow start, progress on the path to personalized medicine is gathering pace. There are a growing number of examples in which personalized medicine is influencing clinical decisions and helping shape healthcare provision. Progress in oncology is rapid and likely to continue apace. Successes outside of oncology are still limited, though, and only time will tell how broadly applicable personalized medicine will become. Updating the regulatory and legislative framework to remove barriers to

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