**Inhibition of Invasion in Treatment of Glioma**

88 Novel Therapeutic Concepts in Targeting Glioma

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inflammatory response leads to derepression of c/ebp Beta and down-regulation of

**6** 

*Brazil* 

**Molecular Targets:** 

*University of São Paulo* 

**Inhibition of Tumor Cell Invasion** 

Raquel Brandão Haga and Silvya Stuchi Maria-Engler\*

*Department of Clinical Chemistry and Toxicology, School of Pharmaceutical Sciences,* 

Gliomas are solid brain tumors that arise from glial cells. According to World Health Organization (WHO), they are classified in four grades based in their histological features. Grades I and II are considered low-grade gliomas and grades III and IV, malignant gliomas. In the United States, each year more than 22,000 people are diagnosed with malignant glioma, representing almost 70% of all malignant primary brain tumors in adults (Wen &

Despite years of research, mortality rates are still high for patients diagnosed with malignant gliomas. Glioblastoma multiforme (WHO grade IV) is the most frequent malignant brain tumor in adults. Even with heavy treatment that includes surgery, radiotherapy and adjuvant chemotherapy, the median survival remains in the range of 12-15 months for patients with this type of tumor (Minniti et al., 2009; Jones & Holland, 2010).

Glioblastomas are separated in two main subtypes: primary glioblastomas and secondary glioblastomas. Primary glioblastoma affects preferentially patients older than 50 years old and has genetic alterations as epidermal growth factor receptor (EGFR) amplification and mutation, loss of heterozygosity of chromosome 10q, deletion of the phosphatase and tensin homologue on chromosome 10 (PTEN), and p16 deletion. Secondary glioblastoma starts as low-grade or anaplastic astrocytomas in younger patients and progresses to glioblastoma over the years. Its main alterations involve mutations in *TP53*, overexpression of platelet derived growth factor receptor (PDGFR), changes in p16 and retinoblastoma pathways, and loss of heterozygosity of chromosome 10q. Even morphologically similar, primary and secondary glioblastomas may differ in their response to molecular targeted therapy (Wen & Kesari, 2008).

Choosing the best treatment depends on the type of tumor, position in the brain, its size and its grade. For patients newly diagnosed with brain malignancies, the current standard treatment protocols include maximally surgical resection, followed by chemotherapy concomitant to fractioned radiation therapy of the tumor. Adjuvant chemotherapy for

**1. Introduction** 

**1.1 Current treatment** 

\* Corresponding Author

Kesari, 2008; CBTRUS 2010; Jones & Holland, 2010).
