Thinking Outside the Box about Ras

The Ras oncoproteins are membrane-associated molecular switches that function to transduce extracellular signals to a panoply of intracellular response mechanisms. Activating mutations in ras genes are present in 15% of all cancers and perhaps as many as 30% of metastatic human cancers. Accordingly, considerable effort has been expended in understanding how Ras proteins work and, by extension, how their transforming activity can be blocked therapeutically (1–6).