RAS

RAS is a family of three closely related genes, KRAS, HRAS and NRAS, and the proteins they encode. Those proteins sit just inside the cell membrane and relay instructions from the outside world to the machinery that makes a cell grow, divide and move. The US National Cancer Institute's RAS Initiative describes their role in cell signalling as pivotal, which is another way of saying that most of the growth instructions a cell receives pass through them.

A healthy RAS protein works as a switch. It flips rapidly between an active form, bound to a molecule called GTP, and an inactive form bound to GDP, so growth signals arrive as pulses rather than as one continuous shout. A mutation can break the off half of that switch. Mutated RAS is stuck in the active state, ignores the signals telling it to stop, and drives the cell to grow uncontrollably and evade the instructions that would normally kill it.

That makes RAS one of the most common drivers of cancer there is. Mutations in the family are found in roughly a third of all human cancers, and the rate is far higher in some: about 95 percent of pancreatic cancers, 45 percent of colorectal cancers and 35 percent of lung cancers. For decades RAS was called undruggable, because the mutant protein is frozen in its on state and researchers could not find a surface on it that a drug would bind to.