344 CANCER CELL: NOVEMBER 2003 screening studies revealed the broad potential for rapamycin as an antiproliferative agent, they did not uncover the mechanism. Nonetheless, the results define two groups of rapamycin-sensitive cell lines—those whose response correlates with inhibition of mTOR (1 nM)(group 1) and those that require significantly higher concentrations (group 2). Of note, the failure of the group 2 cell lines to respond to low “dose”(1 nM) rapamycin cannot be explained by insufficient blockade of mTOR kinase activity because 1 nM rapamycin was equally effective at inhibiting S6K and 4EBP1 phosphorylation in both groups (Neshat et al., 2001). These data support the notion that mTOR is the biologically relevant target of rapamycin for the tumor lines in group 1, whereas other targets are relevant in group 2.