Future considerations for pediatric cancer survivorship: Translational perspectives from developmental neuroscience

Breakthroughs in modern medicine have increased pediatric cancer survival rates throughout the last several decades. Despite enhanced cure rates, a subset of pediatric cancer survivors exhibit life-long psychological side effects. A large body of work has addressed potential mechanisms for secondary symptoms of anxiety, post-traumatic stress, impaired emotion regulation and cognitive deficits in adults. Yet, absent from many studies are the ways in which cancer treatment can impact the developing brain. Additionally, it remains less known whether typical neurobiological changes during adolescence and early adulthood may potentially buffer or exacerbate some of the known negative cancer survivorship outcomes. This review highlights genetic, animal, and human neuroimaging research across development. We focus on the neural circuitry associated with aversive learning, which matures throughout childhood, adolescence and early adulthood. We argue that along with other individual differences, the precise timing of oncological treatment insults on such neural circuitry may expose particular vulnerabilities for pediatric cancer patients. We also explore other moderators of treatment outcomes, including genetic polymorphisms and neural mechanisms underlying memory and cognitive control. We discuss how neural maturation extending into young adulthood may also provide a sensitive period for intervention to improve psychological and cognitive outcomes in pediatric cancer survivors.