This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Brunner, T. B. Articles by Bernhard, E. J. Search for Related Content PubMed PubMed Citation Articles by Brunner, T. B. Articles by Bernhard, E. J. Related Collections Therapeutics and Targets Therapeutics and Targets: Experimental Therapeutics– Small Molecules

Farnesyltransferase Inhibitors

An Overview of the Results of Preclinical and Clinical Investigations¹

Departments of Radiation Oncology [T. B. B., S. M. H., A. K. G., W. G. M., E. J. B.] and Pathology and Laboratory Medicine [R. J. M.], University of Pennsylvania, Philadelphia, Pennsylvania 19104-6072

This article presents an overview of preclinical studies and clinical trials of a number of independently derived farnesyltransferase inhibitors (FTIs). Potential targets and biological modes of action of FTIs are discussed, and the results of clinical trials are summarized. The significant efficacy of FTIs as single or combined agents in preclinical studies stands in contrast with only moderate effects in clinical Phase II-III trials. These results reveal a substantial gap in the understanding of the complex activity of FTIs and their interactions with cytotoxic agents. We conclude that the rational combination of FTIs with other therapies, taking into account the biological activities of the individual agents, may improve the clinical results obtained with FTIs.

This article has been cited by other articles:

				R. E. Marks, A. W. Ho, C. Robbel, T. Kuna, S. Berk, and T. F. Gajewski Farnesyltransferase inhibitors inhibit T-cell cytokine production at the posttranscriptional level Blood, September 15, 2007; 110(6): 1982 - 1988. [Abstract] [Full Text] [PDF]

				S.-Y. Sun, X. Liu, W. Zou, P. Yue, A. I. Marcus, and F. R. Khuri The Farnesyltransferase Inhibitor Lonafarnib Induces CCAAT/Enhancer-binding Protein Homologous Protein-dependent Expression of Death Receptor 5, Leading to Induction of Apoptosis in Human Cancer Cells J. Biol. Chem., June 29, 2007; 282(26): 18800 - 18809. [Abstract] [Full Text] [PDF]

				Y. Qiu, X. Liu, W. Zou, P. Yue, S. Lonial, F. R. Khuri, and S.-Y. Sun The Farnesyltransferase Inhibitor R115777 Up-regulates the Expression of Death Receptor 5 and Enhances TRAIL-Induced Apoptosis in Human Lung Cancer Cells Cancer Res., May 15, 2007; 67(10): 4973 - 4980. [Abstract] [Full Text] [PDF]

				M. Raponi, J.-L. Harousseau, J. E. Lancet, B. Lowenberg, R. Stone, Y. Zhang, W. Rackoff, Y. Wang, and D. Atkins Identification of Molecular Predictors of Response in a Study of Tipifarnib Treatment in Relapsed and Refractory Acute Myelogenous Leukemia Clin. Cancer Res., April 1, 2007; 13(7): 2254 - 2260. [Abstract] [Full Text] [PDF]

				D. CILLONI, E. MESSA, F. MESSA, S. CARTURAN, I. DEFILIPPI, F. ARRUGA, V. ROSSO, R. CATALANO, E. BRACCO, P. NICOLI, et al. Genetic Abnormalities as Targets for Molecular Therapies in Myelodysplastic Syndromes Ann. N.Y. Acad. Sci., November 1, 2006; 1089(1): 411 - 423. [Abstract] [Full Text] [PDF]

				E. T. Efuet and K. Keyomarsi Farnesyl and Geranylgeranyl Transferase Inhibitors Induce G1 Arrest by Targeting the Proteasome Cancer Res., January 15, 2006; 66(2): 1040 - 1051. [Abstract] [Full Text] [PDF]

				T. B. Brunner, K. A. Cengel, S. M. Hahn, J. Wu, D. L. Fraker, W. G. McKenna, and E. J. Bernhard Pancreatic Cancer Cell Radiation Survival and Prenyltransferase Inhibition: The Role of K-Ras Cancer Res., September 15, 2005; 65(18): 8433 - 8441. [Abstract] [Full Text] [PDF]

				I.-A. Kim, S.-S. Bae, A. Fernandes, J. Wu, R. J. Muschel, W. G. McKenna, M. J. Birnbaum, and E. J. Bernhard Selective Inhibition of Ras, Phosphoinositide 3 Kinase, and Akt Isoforms Increases the Radiosensitivity of Human Carcinoma Cell Lines Cancer Res., September 1, 2005; 65(17): 7902 - 7910. [Abstract] [Full Text] [PDF]

				N. M.G.M. Appels, J. H. Beijnen, and J. H.M. Schellens Development of Farnesyl Transferase Inhibitors: A Review Oncologist, September 1, 2005; 10(8): 565 - 578. [Abstract] [Full Text] [PDF]

				M. W. Graner and D. D. Bigner Chaperone proteins and brain tumors: Potential targets and possible therapeutics Neuro-oncol, July 1, 2005; 7(3): 260 - 278. [Abstract] [PDF]

				C.-L. Gau, J. Kato-Stankiewicz, C. Jiang, S. Miyamoto, L. Guo, and F. Tamanoi Farnesyltransferase inhibitors reverse altered growth and distribution of actin filaments in Tsc-deficient cells via inhibition of both rapamycin-sensitive and -insensitive pathways Mol. Cancer Ther., June 1, 2005; 4(6): 918 - 926. [Abstract] [Full Text] [PDF]

				J. Pan, M. She, Z.-X. Xu, L. Sun, and S.-C. J. Yeung Farnesyltransferase Inhibitors Induce DNA Damage via Reactive Oxygen Species in Human Cancer Cells Cancer Res., May 1, 2005; 65(9): 3671 - 3681. [Abstract] [Full Text] [PDF]

				A. I. Marcus, J. Zhou, A. O'Brate, E. Hamel, J. Wong, M. Nivens, A. El-Naggar, T.-P. Yao, F. R. Khuri, and P. Giannakakou The Synergistic Combination of the Farnesyl Transferase Inhibitor Lonafarnib and Paclitaxel Enhances Tubulin Acetylation and Requires a Functional Tubulin Deacetylase Cancer Res., May 1, 2005; 65(9): 3883 - 3893. [Abstract] [Full Text] [PDF]

				K. Venkatasubbarao, A. Choudary, and J. W. Freeman Farnesyl Transferase Inhibitor (R115777)-Induced Inhibition of STAT3(Tyr705) Phosphorylation in Human Pancreatic Cancer Cell Lines Require Extracellular Signal-Regulated Kinases Cancer Res., April 1, 2005; 65(7): 2861 - 2871. [Abstract] [Full Text] [PDF]

				N. E. Martin, T. B. Brunner, K. D. Kiel, T. F. DeLaney, W. F. Regine, M. Mohiuddin, E. F. Rosato, D. G. Haller, J. P. Stevenson, D. Smith, et al. A Phase I Trial of the Dual Farnesyltransferase and Geranylgeranyltransferase Inhibitor L-778,123 and Radiotherapy for Locally Advanced Pancreatic Cancer Clin. Cancer Res., August 15, 2004; 10(16): 5447 - 5454. [Abstract] [Full Text] [PDF]