Targeting signal transduction

George Weber, Fei Shen, Tamás I. Orbán, Szabolcs Kökeny, Edith Olah

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

This overview provides a concise survey of the main aspects of recent progress in the therapy of cancer. The emphasis is on new treatments with a focus on drugs targeted against the elevated signal transduction observed in all examined animal and human neoplasms. 1. The elevated activity of signal transduction in cancer cells should confer selective advantages to the tumor cell population. 2. The clinical and molecular impact of two clinically significant nucleosides, tiazofurin and ribavirin, is compared. 3. Tiazofurin, developed as an anti-cancer agent, provides a multi-faceted impact on biochemical, molecular biology and clinical action. It is noteworthy that in tissue culture and in leukemic patients it yielded inhibition of IMP dehydrogenase activity, resulting in reduced concentrations of GTP and dGTP. In various systems tiazofurin down-regulated the expression of ras and myc, caused apoptosis and induced differentiation. The final common path of tiazofurin action may well be the reduction of signal transduction activity in the cancer cells. 4. Ribavirin, was developed as an anti-viral drug with a spectrum which includes the hepatitis C virus. In patients with hepatitis C ribavirin is effective in combination with interferon-α. The molecular action of ribavirin also leads to reduction of cellular guanylate concentrations and down-regulation of myc oncogene expression. This drug yields apoptosis and induced differentiation. Ribavirin also down-regulated signal transduction activity. These actions were somewhat similar to those of tiazofurin. 5. Since the two drugs inhibit IMP dehydrogenase at two different ligand sites of the enzyme they may be used in a synergistic way in sequence where tiazofurin is administered intravenously, and ribavirin is given by mouth. The two drugs are also meaningful and interesting experimental tools.

Original languageEnglish (US)
Pages (from-to)47-56
Number of pages10
JournalAdvances in Enzyme Regulation
Volume43
Issue number1
DOIs
StatePublished - Jan 1 2003

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Cancer Research

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