Limits...
Targeting TOR dependence in cancer.

Janes MR, Fruman DA - Oncotarget (2010)

Bottom Line: A challenge in cancer therapy has been to identify targets whose function is essential for survival of malignant cells but not normal cells.This Perspective discusses recent evidence that novel inhibitors of the kinase TOR can provide an unprecedented balance of anti-cancer efficacy and tolerability.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA.

ABSTRACT
A challenge in cancer therapy has been to identify targets whose function is essential for survival of malignant cells but not normal cells. This Perspective discusses recent evidence that novel inhibitors of the kinase TOR can provide an unprecedented balance of anti-cancer efficacy and tolerability.

Show MeSH
Simplified diagram of the PI3K/AKT/TOR signaling network. Red indicates TORC2-dependent steps. Blue indicates TORC1-dependent steps. The arrow between AKT and TORC1 represents a multistep process, in which activated AKT and other inputs from growth factor signaling pathways and nutrients are integrated to control TORC1 activity. Activated S6K mediates feedback inhibition of upstream signaling through several mechanisms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2908250&req=5

Figure 1: Simplified diagram of the PI3K/AKT/TOR signaling network. Red indicates TORC2-dependent steps. Blue indicates TORC1-dependent steps. The arrow between AKT and TORC1 represents a multistep process, in which activated AKT and other inputs from growth factor signaling pathways and nutrients are integrated to control TORC1 activity. Activated S6K mediates feedback inhibition of upstream signaling through several mechanisms.

Mentions: TOR is a conserved Ser/Thr kinase that integrates both extracellular and intracellular signals to regulate cell growth, protein translation and metabolism [8-10]. Mammalian TOR (often termed mTOR) exists in two functionally distinct multi-protein complexes, TOR complex 1 (TORC1) and TOR complex 2 (TORC2). TOR kinase interacts with RAPTOR, LST8, FKBP38, DEPTOR and PRAS40 to form TORC1, or with RICTOR, LST8, SIN1, DEPTOR and PROTOR to form TORC2. The complexity of the signaling network is illustrated by the fact that TORC1 functions downstream of AKT, whereas TORC2 functions upstream (Fig. 1). Recent evidence indicates that both TORC1 and TORC2 function to orchestrate and maintain the excessive proliferative demands of tumorigenic cells [11-14].


Targeting TOR dependence in cancer.

Janes MR, Fruman DA - Oncotarget (2010)

Simplified diagram of the PI3K/AKT/TOR signaling network. Red indicates TORC2-dependent steps. Blue indicates TORC1-dependent steps. The arrow between AKT and TORC1 represents a multistep process, in which activated AKT and other inputs from growth factor signaling pathways and nutrients are integrated to control TORC1 activity. Activated S6K mediates feedback inhibition of upstream signaling through several mechanisms.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2908250&req=5

Figure 1: Simplified diagram of the PI3K/AKT/TOR signaling network. Red indicates TORC2-dependent steps. Blue indicates TORC1-dependent steps. The arrow between AKT and TORC1 represents a multistep process, in which activated AKT and other inputs from growth factor signaling pathways and nutrients are integrated to control TORC1 activity. Activated S6K mediates feedback inhibition of upstream signaling through several mechanisms.
Mentions: TOR is a conserved Ser/Thr kinase that integrates both extracellular and intracellular signals to regulate cell growth, protein translation and metabolism [8-10]. Mammalian TOR (often termed mTOR) exists in two functionally distinct multi-protein complexes, TOR complex 1 (TORC1) and TOR complex 2 (TORC2). TOR kinase interacts with RAPTOR, LST8, FKBP38, DEPTOR and PRAS40 to form TORC1, or with RICTOR, LST8, SIN1, DEPTOR and PROTOR to form TORC2. The complexity of the signaling network is illustrated by the fact that TORC1 functions downstream of AKT, whereas TORC2 functions upstream (Fig. 1). Recent evidence indicates that both TORC1 and TORC2 function to orchestrate and maintain the excessive proliferative demands of tumorigenic cells [11-14].

Bottom Line: A challenge in cancer therapy has been to identify targets whose function is essential for survival of malignant cells but not normal cells.This Perspective discusses recent evidence that novel inhibitors of the kinase TOR can provide an unprecedented balance of anti-cancer efficacy and tolerability.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Biology & Biochemistry, University of California, Irvine, CA 92697, USA.

ABSTRACT
A challenge in cancer therapy has been to identify targets whose function is essential for survival of malignant cells but not normal cells. This Perspective discusses recent evidence that novel inhibitors of the kinase TOR can provide an unprecedented balance of anti-cancer efficacy and tolerability.

Show MeSH