The changing face of cancer therapeutics improved : outcome and decreased toxicity with Molecular Targeted Drugs

Abstract

The treatment of patients with cancer has largely involved the administration of cytotoxic drugs with narrow therapeutic indices, with little selectivity for cancer cells over normal proliferating cells. The primary exception to this has been the successful administration of hormonal manipulation to treat breast and prostate malignancies. The development of hormonal manipulation arose from the observation by Sir George Beatson that breast carcinomas improved after bilateral oophorectomy. This led to the use of Tamoxifen and more recently aromatase inhibitors and oestrogen receptor antagonists. These targeted therapeutics are characterised by their ability to induce selective tumour cell death and achieve patient benefit with low toxicity, and have had a significant impact on the outcome of patients with early and advanced oestrogen receptor positive breast cancer. Further advances in the understanding of tumour cell biology, the sequencing of the human genome, and the characterisation of the molecular differences between malignant and normal cells have, over the past two decades, resulted in the identification of a large number of critically important molecular targets. As with the identification of the importance of oestrogens and the oestrogen receptor, this has accelerated the development of molecularly targeted therapeutics and is rapidly revolutionising cancer medicine (Table 1). This brief review will describe some of the most important advances achieved and will attempt to predict what future cancer therapeutics will entail.