in therapy Farnesyltransferase inhibitors in hematologic malignancies: new horizons

2013 
Abstract Farnesyltransferase inhibitors (FTIs) are small-molecule inhibitors that selectively inhibit farnesylation of a number of intracellular substrate proteins such as Ras. Preclinical work has revealed their ability to effectively inhibit tumor growth across a wide range of malignant phenotypes. Many hematologic malignancies appear to be reasonable disease targets, in that they express relevant biologic targets, such as Ras, Mitogen-Activated Protein Kinase (MAPK), AKT, and others that may depend upon farnesyl protein transferase (FTase) activity to promote proliferation and survival. A host of phase I trials have been recently launched to assess the applicability of FTIs in hematologic malignancies, many of which demonstrate effective enzyme target inhibition, low toxicity, and some clinical responses. As a result, phase II trials have been initiated in a variety of hematologic malignancies and disease settings, in order to further validate clinical activity and to identify downstream signal transduction targets that may be modified by these agents. It is anticipated that these studies will serve to define the optimal roles of FTIs in patients with hematologic malignancies and provide insight into effective methods by which to combine FTIs with other agents.From bloodjournal.hematologylibrary.org by guest on June 11, 2013. For personal use only.
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