Cellular and molecular mechanisms of glioblastoma malignancy: implications in resistance and therapeutic strategies

Publication date: Available online 25 September 2018Source: Seminars in Cancer BiologyAuthor(s): Joana Balça-Silva, Diana Matias, Anália do Carmo, Ana Bela Sarmento-Ribeiro, Maria Celeste Lopes, Vivaldo Moura-NetoAbstractGlioblastoma (GBM) is the more frequent and malignant brain tumour. In spite of all efforts, the median overall survival of GBM patients remains approximately 15 months under therapy.The molecular biology underlying GBM is complex, which highlight the need of specific treatment strategies. In fact, the deregulation of several molecular signalling pathways, the existence of the blood-brain barrier, that makes almost all the chemotherapeutic agents inaccessible to the tumour site, and the existence of a population of stem-like cells known to be responsible for tumour recurrence after therapy, can contribute to GBM chemoresistance.In the present review, we summarize the reliable factors responsible for the failure of the most important chemotherapeutic agents in GBM. Specifically, we describe the utmost important characteristics of the blood-brain barrier (BBB), as well as the genetic, molecular and transcription factors alterations that lead to tumour malignancy, and ultimately their impact on stem-like cell plasticity modulation.Recently, nanocarriers have attracted increasing attention in brain- and tumour-targeted drug-delivery systems, owing to their potential ability to target cell surface specific molecules and to cross the BBB delivering the drug speci...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research