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This issue of PeerView/inFocus^TM reviews data presented at the Chemotherapy Foundation Symposium XX: Innovative Cancer Therapy for Tomorrow, which was held on November 13-16 in New York. The editorial by Edward Chu beautifully summarizes the presentations and discussions highlighted in this issue. It is astonishing to note the outright topical revolutions that have occurred over the past 20 years in this and other symposia. While new chemotherapy agents and combinations rightfully continue to be tested in the laboratory and in the clinic, there is no doubt that we have entered the era of targeted therapy. Never before have the biologic perturbations that characterize cancer connected so transparently to the development of new treatments designed to target and manipulate these abnormalities.

Revolutions and new opportunities require adaptation. When change is managed properly, revolutions can lay foundations for wonderful things to come—the American Revolution provides one such glowing example. So, how has the field of clinical oncology research handled the revolution in cancer biology?

Clinical research must place patient welfare above all other considerations, and it is not surprising that our field is inherently conservative in the interest of safety. However, despite grand pronouncements, clinical trial design has not changed much in the past 20 years, and the process of drug development employs, with few exceptions, paradigms that were developed to test cytotoxic chemotherapy agents. While these paradigms are appropriate to assure patient safety, the informed development of targeted therapy agents requires that we also know about the target and its pathway, and understand how the agent under study affects the target when it exerts a meaningful anti-cancer effect.

What can we do? We cannot necessarily learn from our colleagues in other fields who develop new drugs. The biology of these other diseases frequently is less bewildering and disordered, and surrogates for drug effect are more easily identified. So, it is up to us to incite a "revolution" in cancer drug development worthy of the stunning advances in cancer biology.

The reports from this year's Chemotherapy Foundation Symposium XX indicate that we are navigating the first stages of this revolution. Clinical trials of targeted therapy directed against the epidermal growth factor receptor (EGFR) either require some expression of the receptor by the tumor, or at least retrospectively determine the receptor content. Abundant data from clinical trials clearly show that some patients experience gratifying clinical improvement after treatment with cetuximab or other agents that target EGFR. This is good news. Our patients deserve better treatments that minimize suffering, extend meaningful life and improve prospects for cures. However, what factors determine who will benefit? Why does anyone benefit? Why does not everyone benefit? Can we use predictive markers to better select patients for therapy? Will the analysis of drug effects on targets, pathways, and clinical outcomes identify new targets and strategies that can further improve targeted therapy? How can we design clinical trials that will answer these questions? It is easy to ask these questions, but not so easy to come up with the answers. That is proper, since revolutionary challenges rarely respond to evolutionary answers.

So, here is a revolutionary suggestion: take a cancer biologist to lunch. Do this frequently. Listen, talk, and teach each other your lexicons and your respective frames of reference. Connect the discipline of clinical cancer research with biology to identify the key questions that must be addressed if a new agent or strategy is to have its best chance for success. Identify the best possible preclinical systems to detect drug effects in a clinically relevant setting. Design clinical trials to prospectively test hypotheses that extend beyond determination of the phase II working dose, the description of toxicities, and the treatment of many patients to benefit the fortunate few. Creative and fully informed partnerships with cancer biologists, surgeons, and our patients may permit the thoughtful design of well-executed clinical trials that explicitly and definitively test mechanisms of action in tumor tissue while ascertaining clinical benefit and toxicity. The availability of new tools of analysis, such as genomics and proteomics, provides unprecedented opportunities to understand how drugs work. Remember, EGFR-targeted therapies work in 100% of an appropriately selected patient population. Let the revolution really begin!

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