Targeted therapies in breast cancer: Where are we now?

Over the past several years significant advances have been made in our understanding of a growing number of critical pathways involved in breast cancer. These advances have led to the development of novel therapies that are being collectively known as molecularly targeted in order to highlight their specificity and their interference with key molecular events responsible for the malignant phenotype. Examples of approved targeted agents in breast cancer include agents directed against the human epidermal growth factor receptor 2 (HER2) such as trastuzumab and lapatinib and the anti-VEGF bevacizumab. in addition, there are classes of therapies under evaluation including novel anti-HER2 therapies, agents against other tyrosine kinases including Src and Insulin-Like Growth Factor Receptor agents interfering with critically important signalling pathways such as the PI3K/Akt/mTOR inhibitors and agents that promote apoptosis such as Parp inhibitors and others. The challenges that are being brought by these novel therapies are different from those being faced with conventional chemotherapy. They include the selection of appropriate dose and schedule, safety issues, selection of the patient population most likely to benefit and early readouts of clinical benefit. We will present these novel therapies and will analyse for each target the developmental status of some of the agents as well as target-specific challenges. (C) 2008 Elsevier Ltd. All rights reserved.