2012年欧洲乳腺癌靶向治疗指南

Although significant progress in breast cancer diagnosis and therapy has been made in the last two decades, this disease remains one of the leading causes of death in women.This has spurred research on new and more efficient treatments that overcome the limitations of conventionalchemotherapy. Recently, the term ‘targeted therapies’ has been coined to describe new drugs that have been designedbased on the knowledge of the underlying molecular pathology of the disease.

Generally speaking, targeted therapies come in three “flavours”: (i) hormone receptor antagonists, (ii) monoclonal antibodies, and (iii) inhibitors of catalytic kinase domains. Indeed, the first targeted therapy in oncology was the use of anti-hormonal compounds in oestrogen and progesterone positive breast cancer. However, in this review we will developments of the field. Monoclonal antibodies bind with high specificity to their target antigen on the tumour cell and usually induce complement-mediated phagocytosis Kinase inhibitors often bind to the ATP-binding pocket of the enzyme and thus inhibit its catalytic reaction.

In a recent review, Hanahan and Weinberg have summarised the most conspicuous features of human tumours: sustaining proliferative signalling, evading growth suppression, avoiding immune destruction, enabling replicative immortality, tumour-promoting inflammation, activating invasion and metastasis, inducing angiogenesis, genome instability and mutation, resisting cell death, and deregulating cellular energetics. Although all the hallmarks of cancer are principally treatable with drugs, only three of them are currently exploited for the therapy of breast cancer: 1. inhibition of proliferative cell signalling, 2. interference with DNA repair, and 3. anti-angiogenic therapy.