Investigation of Genetic and Molecular Mechanisms of Second Malignant Neoplasms in a Mouse Model

Second malignant neoplasms (SMNs) are late complications arising after exposure to chemotherapy and radiotherapy, accounting for most of the ~90,000 new cancers that are diagnosed annually in the United States in persons who previously had a histologically distinct malignancy. Unfortunately, the incidence of SMNs is expected to grow as the at-risk population of cancer survivors increases.  This prediction has been borne out with the improved survival of pediatric cancer patients over the last few decades and the increasing numbers of SMNs observed in this population.  Given the absence of validated screening, chemoprevention and treatment strategies applicable to SMNs, we face the possibility that SMNs will mitigate present and future gains in childhood cancer survival.  Therefore, understanding the mechanisms underlying this risk, and defining interventions to reduce it (for example, chemoprevention) is an important investment in the future of childhood cancer survivors.

Clinical studies establish SMNs as a growing problem and highlight the critical need for experimental models in which to study cause, treatment and prevention. Our mouse model, which replicates clinical SMN induction in mice, is a valuable experimental system in which to study approaches for preventing SMNs. Because SMNs are complications that affect childhood cancer survivors as a class and not only specific primary tumors, our work has the potential to have broad impact in pediatric oncology and cancer survivorship.