Following the success of imatinib (Glivec) and trastuzumab (Herceptin), the search is on for more rational therapies. But what are the best targets, and how might they be modulated in cancer cells? Three articles explore these concepts in this issue.

The most advanced situation is discussed by Julian Downward on page 11. He describes the RAS pathway, which is activated in many human cancers in a variety of ways ? from amplification of the growth factor receptor ERBB2, to mutation of RAS itself ? so represents an excellent target for inhibition. Several therapeutic agents that target this pathway are showing promise as anticancer agents in the clinic.

In the second article on page 46, Dario Altieri describes the validation of a therapeutic target, survivin, which is an inhibitor of apoptosis (IAP). Survivin is overexpressed in most human tumours, and its inhibition could improve the apoptotic response to traditional therapeutics, such as chemotherapy and radiotherapy. Strategies for achieving survivin inhibition are being explored at present.

Finally, Patricia Steeg focuses on the process of metastasis on page 55. She suggests that metastatic colonization ? defined as the outgrowth of cancer cells at a distant site ? is the most rational target for cancer therapy, as other processes might already have been completed when the tumour is first detected. Eight metastasis suppressors have been identified, and their upregulation in cancer cells could prevent this final step.

This theme is one that we have come back to again and again in Nature Reviews Cancer, and will no doubt continue to do throughout the coming year. Rationally designed therapies are a great hope for anticancer treatment, but much is still to be learned in terms of both targets and targeting strategies.