PI3K/AKT/mTOR pathway

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The PI3K/AKT/MTOR pathway is an intracellular signalling pathway important in apoptosis and hence cancer[1][2][3][4][5] (e.g. breast cancer[6] and non-small-cell lung cancer)[7] and longevity.[8]

mTOR signaling pathway.[1]

The PI3K/AKT/MTOR pathway contributes to hypertrophic muscle growth. It is activated by IGF1 and has a number of downstream effects which either promote protein synthesis or inhibit protein breakdown.

PI3K activation activates AKT which activates mTOR. ('PDK1' in the diagram is Phosphoinositide-dependent kinase-1.)

In many cancers, this pathway is overactive, thus reducing apoptosis and allowing proliferation. Consequently, some experimental cancer drugs aim to inhibit the signalling sequence at some point.

The PI3K pathway may be overactive because PTEN is faulty or deficient.

See also[edit]

References[edit]

  1. ^ Morgensztern D, McLeod HL (September 2005). "PI3K/Akt/mTOR pathway as a target for cancer therapy". Anti-cancer Drugs 16 (8): 797–803. doi:10.1097/01.cad.0000173476.67239.3b. PMID 16096426. 
  2. ^ Cortot A, Armand JP, Soria JC (January 2006). "[PI3K-AKT-mTOR pathway inhibitors]". Bulletin Du Cancer (in French) 93 (1): 19–26. PMID 16455502. 
  3. ^ Yap TA, Garrett MD, Walton MI, Raynaud F, de Bono JS, Workman P (August 2008). "Targeting the PI3K-AKT-mTOR pathway: progress, pitfalls, and promises". Current Opinion in Pharmacology 8 (4): 393–412. doi:10.1016/j.coph.2008.08.004. PMID 18721898. 
  4. ^ LoPiccolo J, Blumenthal GM, Bernstein WB, Dennis PA (2008). "Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations". Drug Resistance Updates 11 (1–2): 32–50. doi:10.1016/j.drup.2007.11.003. PMC 2442829. PMID 18166498. 
  5. ^ "Drug Development Spotlight: The mTOR's New Clothes?". 2010. 
  6. ^ Di Cosimo S, Scaltriti M, Val D, et al. (June 2007). "The PI3-K/AKT/mTOR pathway as a target for breast cancer therapy". Journal of Clinical Oncology 25 (18S): 3511. 
  7. ^ Alvarez, Manrique; Roman, Eloy; Santos, Edgardo S; Raez, Luis E (2007). "New targets for non-small-cell lung cancer therapy". Expert Review of Anticancer Therapy 7 (10): 1423–37. doi:10.1586/14737140.7.10.1423. PMID 17944567. 
  8. ^ http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0050881