Clinical impact of molecular genetic testing in pediatric oncology

Abstract

Despite remarkable progress in the management of pediatric oncological diseases they remain one of the leading causes of mortality. The disease progression due to tumor resistance, treatment-induced toxic effects and infections complications may contribute to the lethality. New diagnostic technologies facilitate the identification of clinically significant genetic alterations for individualization of therapy approach in order to increase its effectiveness, reduce associated toxicity and improve quality of life of patients and their families. The most promising diagnostic approach is based on next-generation sequencing and includes targeted-, whole exome- and genome sequencing of patients’ blood DNA and tumor tissue. Despite the low rate of detected pathogenic alterations, some of them have prognostic significance, determine sensitivity to anticancer agents and targeted therapy. Moreover, targeted therapy in some cancer types shows benefit over standard therapeutic options. The application of targeted therapy in pediatric patients poses more challenges than in adults. This is due to the absence of established doses, regimens and indications for targeted agents in pediatric clinical trials, risks of associated toxicity and its high cost. This paper summarizes the data on molecular genetic markers, which are potentially helpful in guiding therapy for cancer in children.