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.
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.
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.