TORgeting oncogene addiction for cancer therapy.
The PI3K-Akt-mTOR growth-regulating pathway is conserved from mammals to flies and hyperactivated in many cancers. Accordingly, rapamycin analogs, which are inhibitors of mTOR-Raptor signaling, have recently garnered much interest as potential therapeutic agents against cancer. However, due to the heterogeneity of tumors, prior knowledge of the genetic and biochemical background of cancer cells will be required for effective targeted therapy. Thus, the identification of biological markers against activated oncogenic pathways is needed. In the January issue of Nature Medicine, Thomas et al. identify the loss of VHL tumor suppressor gene as a potential determining factor in tumor sensitivity to rapamycin.
Choo
Andrew Y
AY
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Blenis
John
J
D000818:Animals; D058534:Class I Phosphatidylinositol 3-Kinases; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D009857:Oncogenes / Q000235:genetics*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D020123:Sirolimus / Q000494:pharmacology* / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics / Q000378:metabolism*
D058534:Class I Phosphatidylinositol 3-Kinases; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C546842:MTOR protein, human; C484760:PIK3CA protein, human