Kinase inhibitors: vice becomes virtue.

In this issue of Cancer Cell, Fan and coworkers describe a novel inhibitor of PI3 kinase (PI3K) that potently interferes with the growth of glioma cells. They show that the efficacy of this inhibitor results from dual, synergistic activity against the p110alpha subunit of PI3K and against TOR. Although p110alpha and TOR belong to the same signaling pathway, they both must be inactivated because of the need to silence the regulatory feedback loop that remains unaffected by monospecific inhibitors. The new PI3K inhibitor achieves the effects of combination therapy as a single agent by fortuitously hitting two critical targets.