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Multilevel modulation of the mevalonate and protein-prenylation circuitries as a novel strategy for anticancer

Panagiotis A Konstantinopoulos1, Athanasios G Papavassiliou

  • 1Department of Biological Chemistry, Medical School, University of Athens, 11527 Athens, Greece.

Trends in Pharmacological Sciences
|December 8, 2006
PubMed

Insights

Targeting the mevalonate and protein-prenylation pathways shows promise for cancer therapy. Combining inhibitors may improve clinical effectiveness against various malignancies, overcoming disappointing monotherapy results.

Area of Science:

  • Biochemistry
  • Oncology
  • Pharmacology

Background:

  • The mevalonate pathway and protein prenylation are crucial in carcinogenesis.
  • Enzymes in these pathways are targets for anticancer drug development.
  • Preclinical studies show promise, but clinical monotherapy trials have yielded disappointing results.

Purpose of the Study:

  • To review the role of mevalonate and protein prenylation in cancer.
  • To evaluate the clinical efficacy of targeting these pathways.
  • To propose combination strategies for improved anticancer therapy.

Main Methods:

  • Literature review of preclinical and clinical studies.
  • Analysis of drug development targeting isoprenoid biosynthesis and protein prenylation.
  • Evaluation of combination therapy approaches.

Main Results:

  • Monotherapy with inhibitors of these pathways has shown limited clinical success.
  • Preclinical data suggests significant anticancer activity.
  • The need for alternative therapeutic strategies is evident.

Conclusions:

  • Targeting the mevalonate and protein prenylation pathways remains a valid strategy.
  • Combination therapies involving isoprenoid biosynthesis and prenylation inhibitors may offer improved clinical outcomes.
  • Further research into rational drug combinations is warranted for effective anticancer treatment.

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