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Targeting Rho GTPase signaling for cancer therapy.

Abstract
Accumulating evidence from basic and clinical studies supports the concept that signaling pathways downstream of Rho GTPases play important roles in tumor development and progression. As a result, there has been considerable interest in the possibility that specific proteins in these signal transduction pathways could be potential targets for cancer therapy. A number of inhibitors targeting critical effector proteins, activators or the Rho GTPases themselves, have been developed. We will review the strategies currently being used to develop inhibitors of Rho GTPases and downstream signaling kinases and discuss candidate entities. Although molecularly targeted drugs that inhibit Rho GTPase signaling have not yet been widely adopted for clinical use, their potential value as cancer therapeutics continues to drive considerable pharmaceutical research and development.
AuthorsKaterina Mardilovich, Michael F Olson, Mark Baugh
JournalFuture oncology (London, England) (Future Oncol) Vol. 8 Issue 2 Pg. 165-77 (Feb 2012) ISSN: 1744-8301 [Electronic] England
PMID22335581 (Publication Type: Journal Article, Review)
Chemical References
  • Antineoplastic Agents
  • Enzyme Inhibitors
  • Guanine Nucleotide Exchange Factors
  • Lim Kinases
  • Protein-Serine-Threonine Kinases
  • p21-Activated Kinases
  • rho-Associated Kinases
  • rho GTP-Binding Proteins
Topics
  • Animals
  • Antineoplastic Agents (pharmacology, therapeutic use)
  • Cytoskeleton (metabolism)
  • Enzyme Activation (drug effects)
  • Enzyme Inhibitors (pharmacology, therapeutic use)
  • Guanine Nucleotide Exchange Factors (antagonists & inhibitors)
  • Humans
  • Lim Kinases (antagonists & inhibitors)
  • Molecular Targeted Therapy
  • Neoplasms (drug therapy, enzymology)
  • Protein Processing, Post-Translational (drug effects)
  • Protein-Serine-Threonine Kinases (antagonists & inhibitors)
  • Signal Transduction (drug effects)
  • p21-Activated Kinases (antagonists & inhibitors)
  • rho GTP-Binding Proteins (antagonists & inhibitors, metabolism)
  • rho-Associated Kinases (antagonists & inhibitors)

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