Investigation of new therapeutic targets for medulloblastomas classified according to the molecular subgroups.

Abstract

Brain tumors are the second most frequent (after leukemia) and related to death caused by cancer in infants. Medulloblastoma is a brain malignant tumor most common in childhood and have a free-disease survival rate up to 80%. The standard treatment is surgery,radiotherapy (usually in infants older thant 3 years) and chemiotherapy. Recently,based on a transcription and mutational profile data described on a cohort study, was elucidated 4 distincts molecular subgroups of medulloblastomas. Besides the genomics and transcriptional variations between primary samples, the researchers consider that medulloblastomas is composed by 4 main subgroups: WNT,SHH, Group 3 and Group 4. Each one have citogenetics,mutationals and transcriptionals profiles almost completely distincts. Although, they are different in demographic feature (distribution and incidence), clinical and prognosis. The description of these 4 subgroups altered the sight and study of researchers,both in laboratory and clinical trials management. Before,considered and treated as a single tumor, now divided in 4 distincts neoplasias that need alternative treatment.Through molecular biology tools as PCR-Array and Western-blot, this project aims to characterize the cell lines UW402,UW473 and ONS-76 and patient's samples of medulloblastoma according to the new molecular subgroups. It will be investigated new therapeutic targets using the same classification. It will be validated the effect in vitro of inhibitors related to each molecular pathway. This results will be compared with the results obtained from standard chemiotherapics drugs.