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Targeting Hyperactive Ras Signaling in Pediatric Cancer
Anya Levinson1,2, Kevin Shannon1,2, Benjamin J Huang3,4
1Department of Pediatrics, University of California San Francisco, San Francisco, California 94158, USA.
Cold Spring Harbor Perspectives in Medicine
|July 15, 2024
Summary
RAS mutations drive many pediatric cancers. Targeted therapies inhibiting Ras pathways show promise, but drug resistance necessitates combination approaches and better preclinical models for childhood cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Somatic RAS mutations (KRAS, NRAS, HRAS) are frequent drivers in pediatric and adult cancers, with distinct tissue specificities.
- Germline NF1 and RAS mutations in children with RASopathies offer insights into Ras biology and increased cancer risk.
Purpose of the Study:
- To review targeted therapeutic strategies for pediatric cancers with NF1 or RAS mutations.
- To discuss challenges in drug resistance and the development of preclinical models.
Main Methods:
- Review of current literature on RAS mutations in cancer.
- Analysis of targeted therapeutic strategies and drug resistance mechanisms.
- Discussion of preclinical model development for pediatric oncology.
Main Results:
- Targeted therapies include inhibiting Ras effector pathways, Ras signal output, and Ras posttranslational modifications/trafficking.
- Acquired drug resistance is a significant challenge, but combination therapies show promise.
- Development of predictive preclinical models for childhood cancers is a high priority.
Conclusions:
- Targeted therapies offer promising avenues for pediatric cancers with RAS pathway alterations.
- Overcoming drug resistance requires rational drug combinations and advanced preclinical models.
- Further research into Ras biology and therapeutic targeting is crucial for improving outcomes in pediatric oncology.
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