PI3K/AKT/mTOR pathway
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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]
PI3K activation activates AKT which activates mTOR. ('PDK1' in the diagram is Phosphoinositide-dependent kinase-1.)
In many cancers this pathway is overactive reducing apoptosis and allowing proliferation. Thus 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
- PI3K inhibitor
- Akt inhibitor : Miltefosine, In 2007 VQD-002 had a phase I trial.[8] In 2010 Perifosine has reached phase II.[9]
- mTOR inhibitor
- Akt/PKB signaling pathway
- [2] shows a different PI3K pathway (PI3K->Rac1->MEKKs)
- Signal transduction v1.png shows a PI3K->PKC->NF-kappaB pathway
References
- ^ 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.
- ^ Cortot A, Armand JP, Soria JC (January 2006). "[PI3K-AKT-mTOR pathway inhibitors"] (in French). Bulletin Du Cancer 93 (1): 19–26. PMID 16455502. http://www.john-libbey-eurotext.fr/medline.md?issn=0007-4551&vol=93&iss=1&page=19.
- ^ 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.
- ^ 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. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2442829.
- ^ "Drug Development Spotlight: The mTOR's New Clothes?". 2010. http://seekingalpha.com/article/238280-drug-development-spotlight-the-mtor-s-new-clothes.
- ^ 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. http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=47&abstractID=32846.
- ^ 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.
- ^ http://www.emaxhealth.com/95/11480.html VioQuest Pharmaceuticals Announces Phase I/IIa Trial For Akt Inhibitor VQD-002. Apr 2007
- ^ June 7, 2010: Presentation at the American Society of Clinical Oncology annual meeting of Phase I data on single agent perifosine in the treatment of recurrent pediatric solid tumors, including patients with advanced brain tumors and neuroblastoma. also Phase II trial of the novel oral Akt inhibitor perifosine in relapsed and/or refractory Waldenstrom macroglobulinemia (WM).
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