Inhibiting ras signaling in the therapy of breast cancer

Tianhong Li, Joseph A. Sparano

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Ras is a small guanosine triphosphate-binding protein that plays an important role in signal transduction pathways that influence cellular proliferation, apoptosis, cytoskeletal organization, and other important biological processes. Prenylation of Ras proteins by the enzyme farnesyltransferase renders the protein hydrophobic, causing localization to the inner surface of the cell membrane, where it exerts its biological effects. Ras mutations that result in constitutive activation of the Ras pathway are common in certain human cancers, and transfection of cell lines with mutant Ras renders them tumorigenic. Farnesyltransferase inhibitors (FTIs) were initially developed to inhibit growth of cancers harboring Ras mutations, but preclinical data suggests that they also have antiproliferative effects in cell lines with wild-type Ras. Preclinical data suggest that FTIs have antiproliferative and antitumor effects in breast cancer cell lines, but the precise target(s) remain to be defined. One phase II trial has demonstrated that one orally administered FTI has significant antitumor activity in metastatic breast cancer. In addition, preclinical evidence suggests that FTIs may augment the activity of cytotoxic agents and hormonal therapy. Clinical trials are currently underway evaluating whether these agents have a useful role in the management of advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)405-416
Number of pages12
JournalClinical Breast Cancer
Volume3
Issue number6
StatePublished - 2003
Externally publishedYes

Fingerprint

Farnesyltranstransferase
Breast Neoplasms
Cell Line
Prenylation
Biological Phenomena
ras Proteins
Mutation
Cytotoxins
Therapeutics
Guanosine Triphosphate
Transfection
Signal Transduction
Neoplasms
Carrier Proteins
Cell Proliferation
Cell Membrane
Clinical Trials
Apoptosis
Enzymes
Growth

Keywords

  • Combination therapy
  • Farnesyltransferase inhibitor
  • G protein
  • Ras/Raf pathway
  • Signal transduction

ASJC Scopus subject areas

  • Cancer Research

Cite this

Inhibiting ras signaling in the therapy of breast cancer. / Li, Tianhong; Sparano, Joseph A.

In: Clinical Breast Cancer, Vol. 3, No. 6, 2003, p. 405-416.

Research output: Contribution to journalArticle

Li, Tianhong ; Sparano, Joseph A. / Inhibiting ras signaling in the therapy of breast cancer. In: Clinical Breast Cancer. 2003 ; Vol. 3, No. 6. pp. 405-416.
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