[Can defective TGF-Beta signaling be an Achilles heel in human cancer?].

Survival signals in cancer cells activate mTOR-the mammalian target of rapamycin. mTOR suppresses TGF-beta signals that arrest cell cycle progression in late G1-thus activated mTOR prevents cell cycle arrest at a checkpoint mediated by TGF-beta. Rapamycin treatment resurrects TGF-beta signals causing G1 arrest. Defects in TGF-beta signaling are common in human cancer, and ironically, cancer cells with defective TGF-beta signaling that do not arrest in G1, instead undergo apoptosis when treated with rapamycin. Thus, defective TGF-beta signaling may represent an Achilles heel for rational therapeutic targeting of cancer cells using rapamycin-based strategies.