Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia
| Autor: | P. L. Tazzari, Roberta Bortul, Camilla Evangelisti, Maria Nyakern, Giovanna Tabellini, Am Martelli, Lucio Cocco |
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| Přispěvatelé: | Martelli AM, Nyakern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C, Cocco L. |
| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Biology Targeted molecular therapy Models Biological Signal transduction network Phosphatidylinositol 3-Kinases hemic and lymphatic diseases 3-phosphorylated inositol lipid medicine Humans Protein kinase B Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Akt/PKB signaling pathway Myeloid leukemia Apoptosi Hematology medicine.disease Leukemia B vitamins Oncology Leukemia Myeloid Drug resistance Immunology Acute Disease Cancer research Phosphorylation Signal transduction Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Leukemia 20:6 (2006): 911–928. info:cnr-pdr/source/autori:A.M. MARTELLI, M. NYAKERN, G. TABELLINI, R. BORTUL, P.L. TAZZARI, C. EVANGELISTI, L. COCCO,/titolo:Phosphoinositide 3-kinase%2FAkt signaling pathway and its therapeutical implications for human acute myeloid leukaemia,/doi:/rivista:Leukemia/anno:2006/pagina_da:911/pagina_a:928/intervallo_pagine:911–928/volume:20:6 |
| ISSN: | 0887-6924 |
| Popis: | The phosphoinositide 3-kinase (PI3K)/Akt signaling pathway is crucial to many aspects of cell growth, survival and apoptosis, and its constitutive activation has been implicated in the both the pathogenesis and the progression of a wide variety of neoplasias. Hence, this pathway is an attractive target for the development of novel anticancer strategies. Recent studies showed that PI3K/Akt signaling is frequently activated in acute myeloid leukemia (AML) patient blasts and strongly contributes to proliferation, survival and drug resistance of these cells. Upregulation of the PI3K/Akt network in AML may be due to several reasons, including FLT3, Ras or c-Kit mutations. Small molecules designed to selectively target key components of this signal transduction cascade induce apoptosis and/or markedly increase conventional drug sensitivity of AML blasts in vitro. Thus, inhibitory molecules are currently being developed for clinical use either as single agents or in combination with conventional therapies. However, the PI3K/Akt pathway is important for many physiological cellular functions and, in particular, for insulin signaling, so that its blockade in vivo might cause severe systemic side effects. In this review, we summarize the existing knowledge about PI3K/Akt signaling in AML cells and we examine the rationale for targeting this fundamental signal transduction network by means of selective pharmacological inhibitors. |
| Databáze: | OpenAIRE |
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