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Publication : Targeting oncogenic Ras signaling in hematologic malignancies.

First Author  Ward AF Year  2012
Journal  Blood Volume  120
Issue  17 Pages  3397-406
PubMed ID  22898602 Mgi Jnum  J:191819
Mgi Id  MGI:5463163 Doi  10.1182/blood-2012-05-378596
Citation  Ward AF, et al. (2012) Targeting oncogenic Ras signaling in hematologic malignancies. Blood 120(17):3397-406
abstractText  Ras proteins are critical nodes in cellular signaling that integrate inputs from activated cell surface receptors and other stimuli to modulate cell fate through a complex network of effector pathways. Oncogenic RAS mutations are found in approximately 25% of human cancers and are highly prevalent in hematopoietic malignancies. Because of their structural and biochemical properties, oncogenic Ras proteins are exceedingly difficult targets for rational drug discovery, and no mechanism-based therapies exist for cancers with RAS mutations. This article reviews the properties of normal and oncogenic Ras proteins, the prevalence and likely pathogenic role of NRAS, KRAS, and NF1 mutations in hematopoietic malignancies, relevant animal models of these cancers, and implications for drug discovery. Because hematologic malignancies are experimentally tractable, they are especially valuable platforms for addressing the fundamental question of how to reverse the adverse biochemical output of oncogenic Ras in cancer.
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