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Clinical-translational approaches to the Nm23-H1 metastasis suppressor.

Abstract
Nm23-H1 significantly reduces metastasis without effects on primary tumor size and was the first discovered metastasis suppressor gene. At least three mechanisms are thought to contribute to the metastasis-suppressive effect of Nm23-H1: (a) its histidine kinase activity toward ATP-citrate lyase, aldolase C, and the kinase suppressor of ras, with the last inactivating mitogen-activated protein kinase signaling; (b) binding proteins that titer out "free" Nm23-H1 and inhibit its ability to suppress metastasis; and (c) altered gene expression downstream of Nm23-H1, particularly an inverse association with the lysophosphatidic acid receptor endothelial differentiation gene-28 (EDG2). Most metastasis suppressor genes, including Nm23-H1, affect metastatic colonization, which is the outgrowth of tumor cells in distant locations; therefore, they are of high translational interest. A phase II trial is ongoing to test the hypothesis that a compound, high-dose medroxyprogesterone acetate (MPA), used as an unconventional gluocorticoid, will stimulate breast cancer cells to reexpress Nm23-H1 and limit subsequent metastatic colonization.
AuthorsPatricia S Steeg, Christine E Horak, Kathy D Miller
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 14 Issue 16 Pg. 5006-12 (Aug 15 2008) ISSN: 1078-0432 [Print] United States
PMID18698018 (Publication Type: Journal Article, Review)
Chemical References
  • Antineoplastic Agents
  • NM23 Nucleoside Diphosphate Kinases
Topics
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Clinical Trials, Phase II as Topic
  • Humans
  • NM23 Nucleoside Diphosphate Kinases (drug effects, physiology)
  • Neoplasm Invasiveness (genetics)
  • Neoplasms (drug therapy, enzymology)
  • Signal Transduction (drug effects, physiology)

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