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Ras processing as a therapeutic target in hematologic malignancies
Doan Thuy Le1, Kevin M Shannon
1Department of Pediatrics and Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California 94143-0519, USA.
Abstract:
Knowledge of signal transduction pathways has uncovered therapeutic targets for cancer. Based on genetic and biochemical studies of leukemia cells, inhibiting hyperactive Ras represents a rational therapeutic strategy for many hematologic malignancies. Because posttranslational processing by farnesyltransferase is essential for transformation by oncogenic Ras, specific inhibitors of this enzyme are being evaluated as cancer therapeutics. The authors review recent laboratory insights on farnesyltransferase biology and on the development of inhibitors, summarize preclinical and clinical data in myeloid malignancies, and briefly discuss other strategies of interfering with hyperactive Ras.
Insights
Inhibiting farnesyltransferase, which processes oncogenic Ras, is a promising cancer therapy. This review covers farnesyltransferase inhibitors and their efficacy in myeloid malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Signal transduction pathways are crucial in cancer development.
- Hyperactive Ras signaling drives many hematologic malignancies.
- Posttranslational processing of Ras by farnesyltransferase is essential for its oncogenic activity.
Purpose of the Study:
- To review the biological insights into farnesyltransferase.
- To discuss the development of farnesyltransferase inhibitors.
- To summarize preclinical and clinical data on these inhibitors in myeloid malignancies.
Main Methods:
- Review of laboratory studies on farnesyltransferase.
- Analysis of preclinical and clinical trial data.
- Discussion of alternative strategies targeting Ras.
Main Results:
- Farnesyltransferase inhibition is a rational therapeutic strategy for Ras-driven cancers.
- Specific inhibitors are under evaluation as cancer therapeutics.
- Preclinical and clinical data in myeloid malignancies are summarized.
Conclusions:
- Farnesyltransferase inhibitors represent a promising therapeutic avenue for hematologic malignancies.
- Targeting Ras posttranslational processing offers a viable strategy.
- Further research into Ras-targeting therapies is warranted.