Targeting the Process of Farynesylation for Therapy of Hematologic Malignancies

Judith   E.   Karp; Jeffrey   E.   Lancet

Abstract

In sum, the FTIs are signal transduction inhibitors that display promising clinical activity against a broad spectrum of malignancies. We are just beginning to explore and elucidate the mechanisms by which transformed cells respond to FTIs and the optimal settings in which they do so. The clinical trials that are currently in progress and under development will provide the critical foundations for defining the optimal roles of FTIs in patients with AML and other hematologic disorders. The correlative laboratory studies to define the mechanisms by which FTIs alter cellular metabolism and modulate the activities of specific signaling pathways in both normal and malignant marrow precursors are a pivotal part of this effort. What we learn about FTIs in the clinic and the laboratory will apply broadly to the effective and safe application of all signal transduction inhibitors.

Keywords: transduction pathways, farnesyl protein transferase, oncoproteins, Myelodysplasias, Phosphatidylinositol-3 Kinase

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