Inhibition of malignant glioma growth by blocking p21RAS processing
摘要
Introduction: The application of Ras inhibition as a therapeutic strategy against human malignant gliomas follows from studies in our laboratory and elsewhere, which indicate that the proliferation of these tumors is in part driven by excessive activation of Ras-mediated pathways. Ras comprises a family of G-proteins which form key elements in the signal transduction cascade of a variety of growth factors and have been associated with tumorigenesis of at least 30%of human neoplasms. Recent studies show that Ras is overactivated in malignant gliomas and, consequently, that anti-Ras-therapy might represent a promising approach to block the growth of these malignancies. In our study we evaluated the antiproliferative potential of three novel highly selective peptidomimetic inhibitors of p21-Ras processing (FTI-277, GGTI-286 and FTI-298).