The study investigates the enhanced sensitivity of PTEN-deficient tumors to inhibition of the FRAP/mTOR pathway. Using isogenic PTEN+/+ and PTEN−/− mouse cells and human cancer cells, the researchers found that PTEN null cells were more sensitive to the growth-inhibitory effects of the rapamycin derivative CCI-779. This sensitivity was attributed to increased S6 kinase activity and phosphorylation of ribosomal S6 protein, indicating activation of the FRAP/mTOR pathway in these cells. The results suggest that FRAP/mTOR inhibitors may be effective in treating PTEN null human cancers, as they can block tumor growth and induce apoptosis. Additionally, the study shows that the enhanced sensitivity to mTOR inhibition in PTEN null cells is not due to differences in biochemical blockade of the pathway, as S6 phosphorylation was inhibited in both sensitive and resistant cell lines. These findings provide a rationale for further clinical testing of FRAP/mTOR inhibitors in PTEN null cancers.The study investigates the enhanced sensitivity of PTEN-deficient tumors to inhibition of the FRAP/mTOR pathway. Using isogenic PTEN+/+ and PTEN−/− mouse cells and human cancer cells, the researchers found that PTEN null cells were more sensitive to the growth-inhibitory effects of the rapamycin derivative CCI-779. This sensitivity was attributed to increased S6 kinase activity and phosphorylation of ribosomal S6 protein, indicating activation of the FRAP/mTOR pathway in these cells. The results suggest that FRAP/mTOR inhibitors may be effective in treating PTEN null human cancers, as they can block tumor growth and induce apoptosis. Additionally, the study shows that the enhanced sensitivity to mTOR inhibition in PTEN null cells is not due to differences in biochemical blockade of the pathway, as S6 phosphorylation was inhibited in both sensitive and resistant cell lines. These findings provide a rationale for further clinical testing of FRAP/mTOR inhibitors in PTEN null cancers.