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.

RETRACTED ARTICLE: ERK1/2-Nanog signaling pathway enhances CD44(+) cancer stem-like cell phenotypes and epithelial-to-mesenchymal transition in head and neck squamous cell carcinomas

“…A small number of CSCs were able to form tumors in non-obese diabetic/severe combined immunodeficient mice in vivo 5 . Interest in CSCs is rapidly increasing during the recent years, and existence of such cells in various of tumors has been verified including prostate 6 , melanoma 7 , lung 8 , liver 9 , breast 10 , brain 11 , pancreas 12 , ovary 13 , mesenchymal carcinomas, 14 and head and neck 15 . In 2007, Prince et al 16 first identified a cellular subpopulation in head and neck tumors expressing the surface marker CD44 with stem-like characteristics; these cells were capable of reproducing when implanted into immunosuppressed mice.…”

The Role of Rho GTPases in Motility and Invasion of Glioblastoma Cells

“…Primary brain tumors are a mixture of benign and malignant tumors originating from the brain parenchyma and its surrounding microenvironment [1]. Malignant brain and CNS tumors are the 11 th most common type of cancer and the 3 rd most common cause of cancer mortality [1,2]. Annually, primary brain tumors occur at a frequency of around 7 per 100,000 individuals [2].…”

“…Grade IV astrocytoma, called glioblastoma multiforme (GBM), is the most common aggressive type of astrocytoma as well as the most lethal primary brain tumors. GBM has more pronounced malignant features, including uncontrolled cellular proliferation, increased angiogenesis, and resistance to apoptosis [1][2][3]. Therefore, patients diagnosed with GBM have a very poor prognosis with an average survival of 12-15 months post diagnosis [4,5].…”

MicroRNA in Glioblastoma: An Overview

“…Experimental models indicate that in GB exists a subpopulation of cells possessing the characteristics of neural stem cells that are responsible for continuous proliferation and drug resistance [ 54 , 55 ]. miRNA profiling revealed that glioma cells have an expression profile remarkably similar to that of embryonic and neural precursor cells and distinct from that of a normal adult brain [ 56 ].…”