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Targeting Tumor Cell Proliferation: mTORC1 and mTORC2

Evaluating mTORC1 and mTORC2 kinase inhibition

Mammalian Target of Rapamycin (mTOR)

Mammalian Target of Rapamycin (mTOR) is an important regulator of energy and nutrient levels in the cell and adapts cell growth according to the level of nutrients available in the environment. A majority of cancers have inappropriate activation of mTOR, promoting unregulated growth and proliferation as well as resistance to anticancer agents.1 Inhibition of mTOR is therefore an attractive therapeutic strategy. Preclinical models have confirmed that inhibition of mTOR impacts tumor cell growth.2 mTOR exists in two complexes, mTORC1 and mTORC2, both of which contribute to tumor cell growth.3 Inhibition of both complexes is proposed to be necessary to provide optimum control of tumor growth and survival, as well as to overcome resistance to existing antitumor agents.4

mTORC1 & mTORC2 kinase inhibition – AstraZenecaOncology.com

 

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References
  1. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell Rev. 2007;12:9-22.
  2. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signaling controls tumour cell growth. Nature. 2006;441:424-430.
  3. Sarbassov DD, Ali SM, Kim D-H. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol. 2004;14:1296-1302.
  4. Sabatini DM. mTOR and cancer: insights into a complex relationship. Nat Rev Cancer. 2006;6:729-734.