Targeting RAS in pediatric cancer: is it becoming a reality?
Angelina V Vaseva1, Marielle E Yohe2
1The Greehy Children's Cancer Research Institute, The University of Texas Health Science Center at San Antonio, San Antonio, Texas.
Purpose Of Review:
The current review aims to highlight the frequency of RAS mutations in pediatric leukemias and solid tumors and to propose strategies for targeting oncogenic RAS in pediatric cancers.
Recent Findings:
The three RAS genes (HRAS, NRAS, and KRAS) comprise the most frequently mutated oncogene family in human cancer. RAS mutations are commonly observed in three of the leading causes of cancer death in the United States, namely lung cancer, pancreatic cancer, and colorectal cancer. The association of RAS mutations with these aggressive malignancies inspired the creation of the National Cancer Institute RAS initiative and spurred intense efforts to develop strategies to inhibit oncogenic RAS, with much recent success. RAS mutations are frequently observed in pediatric cancers; however, recent advances in anti-RAS drug development have yet to translate into pediatric clinical trials.
Summary:
We find that RAS is mutated in common and rare pediatric malignancies and that oncogenic RAS confers a functional dependency in these cancers. Many strategies for targeting RAS are being pursued for malignancies that primarily affect adults and there is a clear need for inclusion of pediatric patients in clinical trials of these agents.
Insights
RAS mutations are frequent in pediatric cancers, driving tumor growth. Current anti-RAS drugs show promise but need to be tested in pediatric clinical trials for these cancers.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- RAS genes (HRAS, NRAS, KRAS) are the most frequently mutated oncogene family in human cancers.
- RAS mutations are prevalent in adult cancers like lung, pancreatic, and colorectal cancers, driving significant research.
- Despite frequent occurrence in pediatric cancers, advances in anti-RAS therapies have not yet reached pediatric clinical trials.
Purpose of the Study:
- To review the frequency of RAS mutations in pediatric leukemias and solid tumors.
- To propose strategies for targeting oncogenic RAS in pediatric cancers.
- To highlight the need for pediatric inclusion in anti-RAS drug development.
Main Methods:
- Literature review of studies on RAS mutations in pediatric malignancies.
- Analysis of current strategies for targeting oncogenic RAS in adult cancers.
- Synthesis of findings to propose pediatric-focused therapeutic approaches.
Main Results:
- RAS mutations are found in both common and rare pediatric malignancies.
- Oncogenic RAS mutations create a functional dependency in pediatric cancer cells.
- Recent successes in anti-RAS drug development for adult cancers are noted.
Conclusions:
- RAS mutations play a significant role in pediatric cancers.
- Pediatric patients with RAS-mutated cancers should be included in clinical trials for targeted therapies.
- Developing and testing novel strategies against oncogenic RAS is crucial for improving pediatric cancer treatment.
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