Anticancer drug targets: approaching angiogenesis

For more than 50 years, a direct strategy dominated the field of cancer therapy. The selected target was the tumor cell itself; any cytotoxic drug that could kill tumor cells in vitro was by definition a candidate for in vivo chemotherapy. It soon became apparent, however, that normal cells could also be susceptible to the same spectrum of drugs. Moreover, because of the inherent genetic instability of neoplastic cells, exposure to chemotherapy eventually results in the selection of drug-resistant clones. The indirect strategy of antiangiogenic therapy provides an alternative that uses the evolving vasculature, which nourishes the growing tumor, as the prime target. With this approach, oncologists no longer need to restrict their attention to the individual cancer cell but may focus on its tissue context in general, and on angiogenesis, the process of blood-vessel formation, in particular. This conceptual framework, which has guided the search for new methods to identify novel anticancer drugs, is the subject of this Perspective.