Gerard Evan knows all about the cancer-promoting properties of the protein Myc. But he couldn't have predicted the result of blocking Myc activity in a living organism. Then a postdoctoral fellow with a nifty tool joined his lab at the University of California, San Francisco. Now, thanks to that innovation, Evan's group has shown that, in mice, inhibition of Myc can reverse cancer with minimal damage to normal tissues — in stark contrast to today's cancer therapies.

Myc functions as a 'super-coordinator' of growth in both healthy tissues and tumours. Cancer researchers generally avoid targeting such 'hub functions' because they are necessary for normal cell function. “You'd kill the tumour, but you'd also kill normal cells,” Evan explains.

Myc regulates thousands of genes, and is expressed at high levels in a dysregulated manner in most human cancers. Directly activating Myc in normal tissues causes tumours in mice, and Evan's lab and others have studied such transgenic models in detail. When Myc is switched off in these Myc-induced cancers, the tumours regress. However, such tumours are a special case. “The problem is that most cancers are not driven by activated Myc, they're driven by different mutations in many other cancer-causing genes,” says Evan. “In such cancers, Myc itself is typically normal and nobody knew whether it had an important role in tumour maintenance.”

Enter postdoctoral fellow Laura Soucek, who had worked extensively with a Myc mutant during her doctoral studies with Sergio Nasi at the University La Sapienza in Rome. This mutant, called Omomyc, acts as a very potent Myc inhibitor. “I was lucky enough to recruit Laura to my lab,” says Evan. “She wanted to keep working on this. I thought it was interesting, but didn't really know where it would go. Bless her, she built a mouse in which she could express Omomyc transiently, at will, in all tissues of the animal.” The mutated Myc gene could be turned on by giving the mice an antibiotic, and switched off by withdrawing drug treatment.

The researchers tested the effect of Myc inhibition in a mouse model of lung cancer, with only modest hope. At best, Evan says, they suspected Myc inhibition would halt tumour growth. Instead, it eradicated tumours altogether (see page 679).

This was promising, but it seemed likely that Myc inhibition would destroy normal proliferating tissues, such as skin, intestine and bone marrow, as do current chemotherapy and radiation treatments. However, when the group examined these tissues, the effects of Myc inhibition were “dramatic, but surprisingly mild”, says Evan. “There was no tissue damage at all. Proliferating tissues just went to sleep.” And despite the 'shutdown' of these tissues, the mice appeared generally healthy. Moreover, the effects of Myc inhibition were quickly reversed when drug administration was halted.

In short, the results showed a clear difference between the response of tumour cells and normal cells to Myc inhibition. “That was completely unexpected and so exciting,” Evan recalls. His lab is currently extending the work to study Myc inhibition in a variety of mouse cancer models to see whether the phenomenon is a general one.

Evan credits Soucek with the initiative to apply her doctoral tool to a mouse. But most lab heads would have considered that pointless, because of Myc's essential role in many normal tissues. Luckily for Soucek, Evan is not most lab heads. “This was her true love,” Evan says. “It was a tool that was looking for a problem.”