Potential Successes and Challenges of Targeted Cancer Therapies

The concept and realization of targeted anticancer therapy (TAT) have existed for at least two decades and continue to expand rapidly. It has become clear that there is no "magic bullet" to cure cancer and that even TATs are unlikely to be successful as single agents, necessitating combination with chemotherapy, radiotherapy, or even other targeting agents. The other promise that has not been fulfilled by TAT is that of reduced toxicity. It was thought that by targeting receptors on or within cells, rather than particular phases of the cell cycle, TATs would not be toxic. However, it turns out that the targets also exist on or within normal cells and that there is even cross-reactivity between receptors on nontarget tissues. All of this results in toxicity, the mechanism of which are the same as the mechanism of action of the drugs, making toxicity reduction or prevention very difficult. This leads to new toxicities with new targeted treatments. Nevertheless, all of the above should not detract from the obvious successes of targeted agents, which have turned several acutely fatal cancers into chronic diseases and rendered some hitherto untreatable cancers into treatable diseases.