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Lonafarnib in cancer therapy

Floriana Morgillo1, Ho-Young Lee

  • 1M. D. Anderson Cancer Center, Department of Thoracic/Head & Neck Medical Oncology, Houston, TX, USA.

Expert Opinion on Investigational Drugs
|May 31, 2006
PubMed

Insights

Farnesyl transferase inhibitors (FTIs) show anticancer activity by targeting Ras proteins. While early trials were promising, their exact mechanism and impact on overall survival require further investigation.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Farnesyl transferase inhibitors (FTIs) were developed to inhibit Ras protein post-translational modification, crucial for tumor progression.
  • Ras mutations are common in cancer, leading to expectations of high therapeutic efficacy for FTIs.

Purpose of the Study:

  • To review the pharmacological and clinical data of FTIs, focusing on lonafarnib (SCH-66336).
  • To explore the mechanisms of action of FTIs beyond Ras inhibition.

Main Methods:

  • Review of pharmacological and clinical trial data (Phase I, II, and III) for FTIs.
  • Analysis of emerging evidence on FTI mechanisms of action.

Main Results:

  • Phase I and II trials demonstrated significant antitumor activity and low toxicity for FTIs.
  • Phase III trials did not show improvement in overall survival, indicating an incomplete understanding of FTI efficacy.

Conclusions:

  • The precise mechanism of FTI action is not fully understood and likely involves modulation of targets beyond Ras.
  • FTIs, including lonafarnib, exhibit anticancer activity through complex pathways, necessitating further research into their therapeutic potential.

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