Rational approaches to targeted
cancer therapy have begun to predominate the pipelines of oncology drug development. Our rapidly increasing understanding of the "wiring" of
tumor cells and the vulnerabilities of such cells that can potentially be exploited through targeted treatments has opened up enormous opportunities for improved
therapies. Accumulating evidence suggests that many of these vulnerabilities reflect states of dependency or "addiction" that are unique to
cancer cells (versus normal cells). Such addiction can arise due to a strict dependency on a single activated oncogene, a cell lineage-specific factor, or even to a non-oncogene, and identifying these "Achilles' heels" within individual
tumors remains an important challenge to the development of targeted
therapies. Recent technology advances that facilitate high-throughput genomic analysis of
tumor specimens and genome-wide RNA interference screening in
cancer cell lines are key among the newly developed tools that are beginning to reveal novel context-dependent therapeutic targets, and the rapidly increasing application of these technologies by a large number of laboratories will undoubtedly lead to more effective
cancer therapies in the near future. Here, we review the various forms of
cancer cell addiction and their relevance to the discovery of novel therapeutic targets.