Targeting the DNA damage response in pediatric malignancies

Abstract

Introduction High levels of DNA damage and mutations in DNA damage response genes creates a high reliance on DNA damage repair in various tumors. This creates a vulnerability for new cancer therapies. Although there is extensive data for the use of these agents in adult tumors, the evaluation of these compounds in the pediatric population remains in the early stages. Areas covered In this review, we discuss the role of the DNA damage response as a therapeutic vulnerability in pediatric malignancies, provide a summary of clinical data for the use of DNA damage response inhibitors in cancer, and review how these compounds can be extended to the pediatric population. Expert opinion A number of pediatric cancers rely on robust DNA damage repair to maintain cell viability. This provides a therapeutic vulnerability in cancer cells resistant to other traditional therapies. Unfortunately, although clinical evaluation of inhibitors of various components of the DNA damage response has been done in adults, pediatric data remains limited. Further studies are needed to evaluate the efficacy of these compounds in the pediatric population.