Targeting survival cascades induced by activation of Ras/Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways for effective leukemia therapy
作者： J A McCubrey , L S Steelman , S L Abrams , F E Bertrand , D E Ludwig
DOI: 10.1038/LEU.2008.27
关键词:
摘要: The Raf/MEK/ERK, PI3K/PTEN/Akt/mTOR and Jak/STAT pathways are frequently activated in leukemia other hematopoietic disorders by upstream mutations cytokine receptors, aberrant chromosomal translocations as well genetic mechanisms. Jak2 kinase is mutated many myeloproliferative disorders. Effective targeting of these may result suppression cell growth death leukemic cells. Furthermore it be possible to combine various chemotherapeutic antibody-based therapies with low molecular weight, membrane-permeable inhibitors which target the ultimately suppress survival pathways, induce apoptosis inhibit growth. In this review, we summarize how key networks important leukemogenesis therapy treatment Targeting additional cascades also improve chronic myelogenous leukemia, resistant BCR-ABL inhibitors. Furthermore, discuss microenvironment stem emerging fields challenges targeted therapies.
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