Drugs tackle cancer in unexpected way.

A promising class of cancer drugs under development may work through a mechanism far different from the one researchers had initially envisioned. Known as farnesyltransferase inhibitors, the drugs thwart an enzyme that was thought to stimulate cell growth by working with mutant forms of a protein called Ras. Mutant Ras proteins appear in many cancers, which is why the inhibitors have stirred so much excitement (SN: 5/3/97, p. 274).

In the March MOLECULAR AND CELLULAR BIOLOGY, however, scientists present evidence suggesting that farnesyltransferase inhibitors check tumor growth by their effects on a protein called RhoB. By preventing farnesyltransferase from modifying RhoB, the drugs allow cells to convert it into a form that somehow limits cell growth, say George C. Prendergast of the Wistar Institute in Philadelphia and his colleagues. The scientists checked this hypothesis by forcing cancer cells to overproduce the growth-limiting form of RhoB. The tumor cells returned to normal, exactly as if they had been treated with farnesyltransferase inhibitors. Understanding the drugs' interactions with RhoB rather than Ras may lead to improved versions, conclude the scientists.