Aberrant signaling pathways in medulloblastomas: a stem cell connection.
Medulloblastoma is a highly malignant primary tumor of the central nervous system. It represents the most frequent type of solid tumor and the leading cause of death related to cancer in early childhood. Current treatment includes surgery, chemotherapy and radiotherapy which may lead to severe cognitive impairment and secondary brain tumors. New perspectives for therapeutic development have emerged with the identification of stem-like cells displaying high tumorigenic potential and increased radio- and chemo-resistance in gliomas. Under the cancer stem cell hypothesis, transformation of neural stem cells and/or granular neuron progenitors of the cerebellum are though to be involved in medulloblastoma development. Dissecting the genetic and molecular alterations associated with this process should significantly impact both basic and applied cancer research. Based on cumulative evidences in the fields of genetics and molecular biology of medulloblastomas, we discuss the possible involvement of developmental signaling pathways as critical biochemical switches determining normal neurogenesis or tumorigenesis. From the clinical viewpoint, modulation of signaling pathways such as TGFβ, regulating neural stem cell proliferation and tumor development, might be attempted as an alternative strategy for future drug development aiming at more efficient therapies and improved clinical outcome of patients with pediatric brain cancers.
Department of Neurology and Neurosurgery, Universidade Federal de São Paulo, SP, Brazil.
Carolina Oliveira
CO
Rodini
Daniela Emi
DE
Suzuki
Adriana Miti
AM
Nakahata
Márcia Cristina Leite
MC
Pereira
Luciana
L
Janjoppi
Silvia Regina Caminada
SR
Toledo
Oswaldo Keith
OK
Okamoto
D002528:Cerebellar Neoplasms / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008527:Medulloblastoma / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D058953:Neural Stem Cells / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics
D016212:Transforming Growth Factor beta