title: Brain Cancer Stem Cells in Adults and Children: Cell Biology and Therapeutic Implications.
abstract: Brain tumors represent some of the most malignant cancers in both children and adults. Current treatment options target the majority of tumor cells but do not adequately target self-renewing cancer stem cells (CSCs). CSCs have been reported to resist the most aggressive radiation and chemotherapies, and give rise to recurrent, treatment-resistant secondary malignancies. With advancing technologies, we now have a better understanding of the genetic, epigenetic and molecular signatures and microenvironmental influences which are useful in distinguishing between distinctly different tumor subtypes. As a result, efforts are now underway to identify and target CSCs within various tumor subtypes based on this foundation. This review discusses progress in CSC biology as it relates to targeted therapies which may be uniquely different between pediatric and adult brain tumors. Studies to date suggest that pediatric brain tumors may benefit more from genetic and epigenetic targeted therapies, while combination treatments aimed specifically at multiple molecular pathways may be more effective in treating adult brain tumors which seem to have a greater propensity towards microenvironmental interactions. Ultimately, CSC targeting approaches in combination with current clinical therapies have the potential to be more effective owing to their ability to compromise CSCs maintenance and the mechanisms which underlie their highly aggressive and deadly nature.
authors.affiliation: School of Pharmacy, Department of Pharmaceutical Sciences, Lebanese American University, Byblos, Lebanon.
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Abou-Antoun
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Hale
authors.affiliation: Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA.|Department of Molecular Medicine, Cleveland Clinic Lerner College of Medicine at Case, Western Reserve University, Cleveland, OH, USA.|Case Comprehensive Cancer Center, Cleveland, OH, USA.
authors.forename: Justin D
authors.initials: JD
authors.lastname: Lathia
authors.affiliation: Department of Neurological Surgery, Section of Pediatric Neurosurgical Oncology, Neurological Institute, Cleveland Clinic, Cleveland, OH, USA. dombros@ccf.org.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Dombrowski
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000235:genetics / Q000503:physiopathology* / Q000628:therapy*; D002648:Child; D002675:Child, Preschool; D019008:Drug Resistance, Neoplasm; D044127:Epigenesis, Genetic; D006801:Humans; D014411:Neoplastic Stem Cells / Q000502:physiology*; D059016:Tumor Microenvironment
keywords: Cancer stem cells; Childhood brain tumors; Epigenetics; Glioblastoma; Microenvironment; Therapeutic implications