Effect of cancer therapy on neural stem cells: implications for cognitive function

Curr Opin Oncol. 2012 Nov;24(6):672-8. doi: 10.1097/CCO.0b013e3283571a8e.

Abstract

Purpose of review: Modern cancer therapies have allowed for a dramatic increase in the survival rates in both children and adults. However, a frequent and unfortunate side-effect of cancer therapy is a long-term decline in neurocognitive function. Specifically, cranial radiation therapy markedly alters memory processes, while chemotherapeutic agents are correlated with deficits in attention, concentration, and speed of information processing. Here, we describe the putative cellular etiologies of cancer treatment-induced cognitive decline, with an emphasis on the role of neural stem and precursor cell dysfunction.

Recent findings: New studies highlight the lasting effects of chemotherapy on memory, executive function, attention, and speed of information processing up to 20 years following chemotherapy. Cognitive decrements are associated with decreased white-matter integrity as well as alterations in stem cell function in humans and rodent models of cancer therapy. Genetic polymorphisms may underlie differential sensitivity of certain individuals to the neurological consequences of chemotherapy. Increasing data support the concept that disruption of normal neural stem and precursor cell function is an important causative factor for the cognitive deficits that result from cancer therapy in both children and adults.

Summary: Further studies are needed to elucidate the role of chemotherapy on cell-intrinsic processes and cellular microenvironments. Further, the effects of the new generation of targeted molecular therapies on neural stem and progenitor cell function remains largely untested. Understanding the mechanisms behind cancer therapy-induced damage to neural stem and precursor cell populations will elucidate neuroprotective and cell replacement strategies aimed at preserving cognition after cancer therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Cognition / drug effects*
  • Cognition / radiation effects
  • Hippocampus / drug effects
  • Hippocampus / pathology
  • Hippocampus / radiation effects
  • Humans
  • Memory Disorders / chemically induced
  • Memory Disorders / physiopathology
  • Neural Stem Cells / drug effects*
  • Neural Stem Cells / radiation effects
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / radiotherapy
  • Radiation Injuries / physiopathology

Substances

  • Antineoplastic Agents