Advertisement

help button home button The Oncologist
HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow eLetters: Submit a response to this article
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article link to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Reprints/Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sebti, S. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sebti, S. M.
The Oncologist, Vol. 8, Suppl 3, 30–38, December 2003
© 2003 AlphaMed Press

Blocked Pathways: FTIs Shut Down Oncogene Signals

Saïd M. Sebti

H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, Tampa, Florida, USA

Correspondence: Saïd M. Sebti, Ph.D., Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, University of South Florida, 12902 Magnolia Drive, Tampa, Florida 33612, USA. Telephone: 813-979-6734; Fax: 813-979-6748; e-mail: sebti{at}mof fitt.usf.edu

Ras proteins play fundamental roles in cell signal transduction pathways that regulate cell growth, differentiation, proliferation, and survival. ras mutations are among the most frequently encountered genetic abnormalities in human cancers and play a key role in tumorigenesis. The enzymatic attachment of a 15- or 20-carbon moiety to the Ras protein through farnesylation or geranylgeranylation, respectively, is a required step in the proper localization and activation of Ras. Inhibition of the catalytic enzymes, farnesyl transferase and geranylgeranyl transferase, is a novel, mechanism-based, targeted approach to cancer therapy development. Geranylgeranyl transferase inhibitors suppress tumor growth by accumulating cells in the G1/S cell cycle phase. One mechanism by which farnesyl transferase inhibitors suppress tumor growth is by inhibiting bipolar spindle formation, thereby blocking progression from prophase to metaphase. Although the exact molecular target responsible for the antitumor activity of farnesyl transferase inhibitors is unclear, at least in some tumor cells, inhibition of phosphoinositide-3-OH kinase/Akt-mediated cell survival pathways may play a critical role. Identifying the farnesylated proteins that are targeted by farnesyl transferase inhibitors and the tumor molecular signatures that dictate which set of patients will respond to farnesyl transferase inhibitors are critical end points for future mechanistic studies.

Key Words. Farnesyl transferase inhibitors • Geranylgeranyl transferase-I inhibitors • Oncogenes • Signal transduction • Targeted therapy




This article has been cited by other articles:


Home page
J Biomol ScreenHome page
C. Granas, B. K. Lundholt, F. Loechel, H.-C. Pedersen, S. P. Bjorn, V. Linde, C. Krogh-Jensen, E.-M. D. Nielsen, M. Praestegaard, and S. J. Nielsen
Identification of RAS-Mitogen-Activated Protein Kinase Signaling Pathway Modulators in an ERF1 Redistribution(R) Screen
J Biomol Screen, June 1, 2006; 11(4): 423 - 434.
[Abstract] [PDF]


Home page
J. Lipid Res.Home page
R. T. Eastman, F. S. Buckner, K. Yokoyama, M. H. Gelb, and W. C. Van Voorhis
Thematic review series: Lipid Posttranslational Modifications. Fighting parasitic disease by blocking protein farnesylation
J. Lipid Res., February 1, 2006; 47(2): 233 - 240.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
C. Dorrell, K. Takenaka, M. D. Minden, R. G. Hawley, and J. E. Dick
Hematopoietic Cell Fate and the Initiation of Leukemic Properties in Primitive Primary Human Cells Are Influenced by Ras Activity and Farnesyltransferase Inhibition
Mol. Cell. Biol., August 15, 2004; 24(16): 6993 - 7002.
[Abstract] [Full Text] [PDF]


Home page
The OncologistHome page
E. K. Rowinsky
Crossing the Cancer Cell Membrane to Improve Clinical Outcomes
Oncologist, December 1, 2003; 8(90003): 1 - 4.
[Full Text] [PDF]




HOME HELP CONTACT US SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
THE ONCOLOGIST STEM CELLS CME ALPHAMED PRESS JOURNALS


Copyright © 2003 by AlphaMed Press.
Advertisement