Insights into pharmacotherapy of malignant glioma in adults

Abstract

Malignant gliomas are the most common primary brain tumors in adults. In the past 10 years significant advances in the treatment of this entity have been made, mainly owing to a better understanding of molecular pathways and biological behavior of the oncogenetic process. This review treats the proven effective and promising approaches with chemotherapy. The standard care for glioblastoma is surgery and concomitant radio- and chemotherapy with temozolomide (TMZ), followed by adjuvant treatment with TMZ. It has been demonstrated to be the most effective treatment protocol. This standardized care allows the application and study of new types of treatment mainly in recurrences and nonresponding patients. Many different approaches have been investigated: the combination of cytotoxic and cytostatic agents as well as molecular targeted therapies have given some encouraging results. Further intensified regimens with TMZ and the local postsurgical application of slow-release polymers loaded with carmustine remain to be defined. The characterization of molecular markers thus becomes particularly important for the stratification of patients raising the possibility to individualize treatment.

Connexin43 confers Temozolomide resistance in human glioma cells by modulating the mitochondrial apoptosis pathway

“…TMZ is currently the most effective chemotherapeutic demonstrating excellent CNS bioavailability (Neyns et al, 2010;Stupp et al, 2005), causing DNA methyl adducts on the N 7 of guanine, N 3 of adenine and O 6 position of guanine, about 70%, 9% and 5% respectively (Villano et al, 2009). The latter DNA adduct is primarily responsible for the cytotoxic effect, however, clinical response toward TMZ is generally short-lived as tumor cell heterogeneity, transformation, genetic instability and selective pressures (Salvati et al, 2009) contribute to the development of chemoresistant tumors (Giese et al, 2003). O-6-methylguanine-DNA methyltransferase (MGMT) can remove toxic TMZ-induced DNA methylation and its expression is correlated to poor TMZ response (Esteller et al, 2000).…”

The adherens junction-associated protein 1 is a negative transcriptional regulator of MAGEA2, which potentiates temozolomide-induced apoptosis in GBM

“…It is an alkylating cytostatic drug, which causes DNA damage and induces cell death. However, clinical response toward TMZ is generally short-lived, possibly due to multiple factors such as tumor cell heterogeneity, resistant glioma stem cells, rapid transformation, genetic instability and selective pressures (9,10). The available data suggest that neither MGMT protein expression levels nor MGMT promoter methylation status is a sufficiently accurate predictor of the sensitivity of the glioma cells to TMZ (11).…”

Transdural spread of glioblastoma multiforme with endonasal growth in a long-term survivor patient: case report and literature review

“…Through this treatment, survival of GBM patients have been increased (15). GBM does not usually show leptomeningeal invasion.…”