From the Editor

This table is a summary of selected “molecularly targeted” agents approved by the FDA in just over a decade. Generating such a list raises the question of what actually constitutes a molecularly targeted agent. For many investigators, the term emphasizes monoclonal antibodies and tyrosine kinase inhibitors (TKIs), as we have in this issue. However, we must recognize that frequently, for our targeted agents, the target(s) is still unknown, and further, one might argue that for older drugs, such as the taxanes and tamoxifen, the target is better defined. Regardless, this list of drugs represents a major success in its expansion of options for our patients. While imatinib revolutionized the therapy of CML and introduced an unprecedented level of optimism in the field, the reality for solid tumors is that targeted therapies have thus far had only limited success. The clinical data presented in seeking their approval remind us of the unenviable challenge the FDA confronts—such as determining whether a 10-day survival advantage warrant a drug's approval. The May 2001 issue of TIME magazine described imatinib as new ammunition in the war against cancer and as a prototype for other therapies. However, over the decade it has become evident that we are still far from identifying the magic bullet both in terms of toxicity and efficacy.

The mechanisms limiting efficacy are the subject of this issue of CCR Focus. Our experts examine drug resistance—to imatinib and related TKIs in CML and GIST and to erlotinib and gefitinib in lung cancer. Turning to the monoclonal antibodies, both validated and hypothesized mechanisms of resistance to cetuximab and trastuzumab are described. Our Guest Editor Lee Ellis highlights these discussions and then clarifies recent arguments about a dark side to resistance to agents such as bevacizumab. We see again the complexity of cancer and the adaptability of cancer cells. As with every issue of CCR Focus, it is our hope that the articles inform and intrigue both the expert in the field and the interested but non-expert observer.