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Background

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The principle of personalized medicine, which aims to deliver a management schedule based on the attributes of the individual rather than on the whole population with the same diagnosis, has always been particularly attractive in oncology. Identification of patients who will receive maximum benefit from aggressive treatment regimens as well as those who will not benefit from standard therapies has the potential to improve cure rates in early disease, reduce the risk of toxicity and improve quality of life in advanced cancer. Historically, however, cancer has largely been treated simply on the basis of the anatomical site and extent of the disease using cytotoxic drugs that cause significant collateral damage through a tendency to identify malignant cells only by their rapid movement through the cell cycle. Prior to 1990, drugs that recognized cancer cells in a more targeted fashion did exist, but their use was largely unselected; for example, the anti-oestrogen tamoxifen was originally given to all breast cancer patients. Its use was only limited to oestrogen receptor-positive patients after retrospective data published some 30 years later showed clear evidence of effectiveness only in this subgroup.

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Use of biomarkers to measure disease course or treatment responsiveness has also largely relied on circulating protein 'tumour markers', which vary significantly from one patient to another in terms of their specificity and clinical utility. Important exceptions are alpha-fetoprotein (AFP) and human chorionic gonadotrophin (hCG), which have gained clinical acceptability as useful prognostic markers of germ cell cancer. The production of trastuzumab, a humanized monoclonal antibody specifically designed to bind to a protein overexpressed on the cell surface in an aggressive subgroup of breast cancers was a pivotal development in oncology. The success of this drug, which combines clinical effectiveness with a preferable toxicity profile to conventional cytotoxics, has been followed by the development of many other antibodies and small molecules designed to match newly identified tumour features.

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Recent developments

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The completion of the Human Genome Project in 2000 heralded a new era in cancer biology. We now know that there are typically between 1000 and 10,000 somatic genetic changes in the genomes of most adult cancers. The mutational landscapes of many tumours have been made publicly available through projects such as The Cancer Genome Atlas project. Identification of the key driver mutations in some tumour types has permitted the development of a number of therapeutic agents that specifically target the aberrant protein product. In current clinical practice the abnormal protein or genetic fault is usually detected using tests developed to detect that specific tumour-associated change. More recently, however, with massive advances in genomic technologies over the last decade, it is now feasible and potentially cost-effective to directly examine the whole DNA sequence of an individual tumour specimen in a timely fashion in order both to predict response to novel targeted therapies and to increase our prognostic accuracy by categorizing disease subtypes at a molecular level....

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