Outcomes for pediatric cancer patients have improved over the last few decades due to advancements in treatments, including those for pediatric brain tumors. However, side effects can still have negative effects on patients long after treatment is complete, and some research focus has shifted to combating these effects. One emerging field to address this issue is Pharmacogenomics, the use of genetic information to predict an individual’s response to specific medications. This can help identify patients at increased risk for treatment related toxicities, guiding medical professionals in treatment decisions. An example of the potential impact of research into pharmacogenomics in pediatric cancers is vincristine. Vincristine is a chemotherapy agent that is used in many treatment protocols, including for low-grade gliomas and medulloblastoma. Vincristine is also associated with significant side effects often resulting in dose reductions. Two different studies have identified a genetic variation in the promoter of the CEP72 gene, rs924607, in both adult and pediatric patients with acute lymphoblastic leukemia. This genetic variation is associated with increased rates of vincristine side effects. The role of this variation has not been evaluated in other cancers, such as low-grade gliomas, medulloblastoma, and rhabdomyosarcoma, despite the wide use of vincristine in these treatment regimens. Using the over 900 pediatric tumor genomes sequenced in the Pediatric Brain Tumor Atlas, this study will help to define the frequency of genetic risks for vincristine-related side effects in patients with a spectrum of diagnoses. This research could serve to prevent reductions in therapy due to toxicity, increasing the likelihood of a positive response to treatment.
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