Furthermore, cancer cells are protected from apoptotic activity, due to mutations such as of p53 or NF-kB. Developments of this enormous subject are reviewed in ref. 57. Killing cancer cells is easy; selection is the problem—to kill them but not normal cells. The discovery of differences of regulation between normal and cancer cells provides potential targets for detection, prognosis and therapy. An emergency exit mechanism that leads to apoptosis may be activated if a normal cell overexpresses a proliferation-related gene. Such a mechanism may have become inactive in a cancer, which might provide the needed difference. Studies of regulation have practical aspects. Drugs such as Gleevec, an inhibitor of an over expressed proliferation-related kinase, are being applied clinically, as are proteasome inhibitors such as PS341. Many other targeted applications are under development, of which a potential anti-cancer therapy initiated in this laboratory provides an example. b-Lapachone, a natural product, increases E2F-1,82 decreases ATP and NAD,83 and selectively causes apoptosis of cancer cells. It is remarkably and specifically effective against tumors implanted in mice, and is now in clinical trials.