An example of a molecule causing much interest in breast cancer treatment is lapatinib, which administered orally. It was designed to hit a subset of the popular Epidermal Growth Factor Receptors (EGFR), which are targeted by other successful agents such as trastuzamab (Herceptin), cetuximab (Erbitux) and gefitinib (Iressa). The first two are monoclonal antibodies, against ErbB2 and ErbB1 respectively, the third is a 'designer' drug. Trials of the combination of antibodies have been promising, so the development of lapatinib to block both receptors via their tyrosine kinase portions is giving rise to optimism. It is a small molecule, like gefitinib, and may have pharmacological advantages over the antibody formulations, such as penetrating the blood-brain barrier.
Early clinical trials with lapatinib suggest that it may hit cancer cells, resistant to other commonly used breast cancer drugs, and to the other EGFR targeting agents, including trastuzamab. Its activity as a single agent is modest, but combination trials already underway are looking promising enough to start randomised comparative large scale investigation. Side effects reported so far suggest a good safety profile, though skin rash, lung and heart effects seen with other members of the drug class will be monitored carefully in the next generation of trials. And, following the example of tamoxifen, it is being tested as a chemo-preventive too.
Dr F. Cardoso from the Jules Bordet Institute, Brussels, who is involved in the drug research comments, "Raloxifene and lapatinib are exciting new drugs which will be of interest in prevent
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Federation of European Cancer Societies