Targeted therapies in solid tumours: pinpointing the tumour's Achilles heel

Abstract

It is now exactly 100 years ago (1908) that Paul Ehrlich, who is regarded as the inventor of the concept of targeted therapy, received the Nobel Prize for Medicine. His initial perception leading to this theory was derived from observations that certain substances are capable of selectively staining either tissues or microorganisms. These observations culminated in the discovery of the inorganic mercury compound arsphenamine (Salvarsan) by Sahachiro Hata in the laboratory of Paul Ehrlich. Salvarsan might be regarded as the first effective "targeted" treatment for syphilis at that time. Tamoxifen (Nolvadex), an anti-estrogen, which was introduced in the early 1970s, was one of the first rationally designed targeted anti-tumour drugs. Since the 1970s a dramatic development of new molecular technologies occurred, culminating, for example, into the Human Genome Project and the public availability of various gene and protein databases, such as the Cancer Genome Anatomy Program established by the National Cancer Institute. Genomics, proteomics, structural genomics, transcriptomics, and high-throughput screening technologies for identification of targeted drugs are now available, which were almost unimaginable only a few years ago. Over 500 kinases are known of which about 250 have been cloned and are available to directly evaluate the activity of novel drug candidates. These technologies in conjunction with bio-informatic and chemical tools allow us to design novel molecules, and consequently tailor drug therapy to specific targets within tumours.