Which strategies will lead to progress in the management of colorectal cancer?

The past decade has seen considerable progress in the treatment of colorectal cancer (CRC) in the United States; whereas in 1996, one agent had been approved for the treatment of CRC, there are now seven approved drugs in the United States. This panoply of options now requires us to refine our approaches to therapy. It apears that the best approach would be to devote ourselves to unraveling the biology of CRC, so that we can both understand its diversity and use that understanding to individualize treatment for patients with this disease. The focus would be to maximize antitumor effects and, when possible, to minimize toxicity. Genetic analyses of tumors, the host, or both should lead to such advances, as preliminary analyses have shown. Optimizing drug combinations and minimizing toxicity has heretofore been mainly empirically rather than scientifically driven. A host of rationally designed new agents are in development. Sorting through those with clinical activity - although a difficult process - should result in additional active agents. One troubling consequence of this new drug development has been the high costs of combination therapies, which may render them unavailable to certain patient segments that could potentially benefit from them. Despite the complexities involved, the pace of progress is accelerating and sustaining that pace must be our highest priority.