[Molecular targeted therapy in colorectal cancer]

A diversity of cytotoxic and molecularly targeting agents are now offered for colorectal cancer; 5-fluorouracil was until recently the only available therapy. Molecular targeting agents inhibit cellular signalling mechanisms that govern tumour cell proliferation and survival.

The article is mainly based on publications identified by searching PubMed, as well as abstracts and presentations at recent international congresses.

Receptor tyrosine kinases are involved in cellular processes such as proliferation and angiogenesis, and signalling activities evoked by these enzymes are targets for pharmacological inhibition. The antibody bevacizumab inhibits angiogenesis. Randomized studies have shown that survival or time to progression of metastatic disease is improved when bevacizumab is combined with cytotoxic drugs (5-fluorouracil with or without irinotecan or oxaliplatin). The antibody cetuximab inhibits activation of a tumour cell growth factor receptor, and was approved for therapy on the basis of a large randomized phase 2 study. A wide array of small-molecular inhibitors of signalling by receptor tyrosine kinases are under clinical investigation, but their therapeutic contribution in metastatic colorectal cancer needs to be clarified. According to Nordic recommendations on the use of molecular targeted agents in combination with chemotherapy for metastatic colorectal cancer, bevacizumab should be considered in the first-line treatment of patients with a good performance status and cetuximab in third-line treatment.