The mitogen-activated protein kinase signaling module as a therapeutic target in hematologic malignancies

摘要: Important insights into the cellular and molecular biology of cancer in general hematologic malignancies particular have been gained past two decades. The genes, their protein products, involved transformation cells from normal to neoplastic, as well progression neoplastic a more aggressive, therapy-resistant phenotype, are being elucidated great detail. However, most malignancies, particularly adult acute leukemias, remain associated with high mortality rates new therapeutic approaches urgently needed. challenge is therefore carefully efficiently translate information effective strategies. clinical success achieved by tyrosine kinase inhibitors, such ST1571 chronic myelogenous leukemia, has stimulated interest for kinase-based signaling pathways targets malignancies. mitogen-activated (MAPK) pathway common point convergence many different mitogenic anti-apoptotic signal transduction hematopoietic, epithelial, can now be clinically targeted highly selective small molecule inhibitors. mounting preclinical evidence anti-leukemic activity MAPK alone or combination pro-apoptotic molecules conventional chemotherapeutic agents provides rationale that inhibition-based treatment strategies could soon enrich our armamentarium against human leukemias.