Tossing monkey wrenches into the clock: New ways of treating cancer

After a decade’s worth of rapid research advances, we begin to understand in detail how a normal mammalian cell decides whether it should grow. Those interested in curing cancer have consumed this information avidly. They believe that an understanding of normal cell cycle control provides them with the key to developing new generations of antitumor therapeutics. At the end of the decade, we now know that the runaway proliferation of a malignant cell is due to minor defects in the machinery that governs normal cell growth and division. On the one hand, this is reassuring, because the root causes of cancer can be pinpointed with precision, ascribed to defective components operating in one or another location in the cellular growth-regulating circuitry. But on the other, the prospects for anticancer drug development have become all the more daunting, since the differences between malignant and normal proliferative control appear to be so small, and thus seem to provide few opportunities for selectively targeting cancer cells while leaving their normal counterparts untouched. The report by Chen et al. (1) in this issue describes one of the first efforts to exploit our newly gained information on mammalian cell cycle control to kill cancer cells. The fact that this is a pioneering effort in this area is itself surprising. In the face of so much information, relatively few researchers have found windows of opportunity for drug development. They have looked for the Achilles heels of cancer cells and been hard-pressed to identify attractive targets. As Chen and coworkers now show, creative interpretation of recent discoveries about the cell cycle clock has revealed a vulnerability, a chink in the armor of the cancer cell. In one sense, the metaphor of a clock is unfortunate: the cell cycle clock does not measure elapsed time. Instead, it operates …