Status Quo—Standard-of-Care Medical and Radiation Therapy for Glioblastoma

Department of Neurology, Yale University School of Medicine, New Haven, CT 06520, USA.
The Cancer Journal (Impact Factor: 4.24). 01/2012; 18(1):12-9. DOI: 10.1097/PPO.0b013e318244d7eb
Source: PubMed


There will be approximately 10,000 new cases of glioblastoma diagnosed in the United States this year alone. Although a relatively rare cancer, these aggressive tumors lead to a disproportionate amount of cancer morbidity and mortality. The current standard treatment for a glioblastoma consists of surgery for cytoreduction and/or biopsy followed by chemoradiation and adjuvant temozolomide. Without treatment, most patients will die of their disease within 3 months of diagnosis. Surgical intervention can extend survival to 9 to 10 months, and this can be lengthened to 12 months with the addition of adjuvant radiation. In a 2005 landmark clinical trial, Stupp et al demonstrated that temozolomide, an oral DNA-alkylating chemotherapeutic agent, when added to radiation, can improve survival to 14.6 months. Although the effect on survival is modest, this treatment course represents a significant improvement over chemotherapy agents widely used for the 3 previous decades. This review will focus on the development of temozolomide and its use along with radiation therapy as the current standard treatment for glioblastoma.

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    • "Radiation therapy is a currently standard treatment for a number of malignancies (Becker & Yu, 2012). The response of a cancer to radiation is described by its radio-sensitivity. "
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    ABSTRACT: Radiation therapy aims to kill cancer cells with a minimum of normal tissue exposure. In an attempt to define the molecular and biochemical changes associated with exposure to radiotherapy, the objective of the present study is to explore the effect of gamma (γ) irradiation on nuclear factor, erythroid 2 (NFE2), P53, stromelysin-1 (matrix metalloproteinase-3) (MMP3), BCL-2 and BAX genes expression in Ehrlich ascites carcinoma (EAC) bearing mice. Various biochemical parameters such as liver function, H2O2, B% and T% lymphocytes, total antioxidants and MDA were investigated to evaluate their usefulness as possible during cancer treatment with radiotherapy. Rats were irradiated with a single whole body Cobalt 60-gamma radiation dose of 0.5 Gy. Sixty-four female mice, weighing 20–25 g were used in this study and divided into three main groups. The first group served as control group, while the second were injected intraperitoneally with EAC then was subdivided into two groups, II A and II B. The latter one (group II B), the animals were exposed to a single dose of 0.5 Gy whole body γ irradiation. The third main group, were irradiated with a single dose of 0.5 Gy whole body γ irradiation. Blood and liver tissue samples were collected at 4, 24 and 96 h post-irradiation. The gene expression levels in the livers of animals from each exposure group were compared individually with that of pooled sham-irradiated animals. MMP3 and NFE2 were overexpressed in liver samples of EAC group post 4, 24 and 96 h of γ irradiation (IIB). On the other hand, P53 and BCL-2 genes were downregulated by using RT-PCR analysis post 4, 24 and 96 h of γ irradiation (IIB). As well as, liver function and MDA were increased significantly in the γ - irradiation group (3rd group) when compared to control mice (1st group). Gamma irradiation 3rd group revealed increase in the level of T% and B% lymphocytes. According to the obtained results, both γ rays and time period alter the genes expression and most of the investigated biochemical parameters.
    Full-text · Article · Apr 2014
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    • "Glioblastoma multiforme (GBM) is the most malignant form of primary astrocytic brain tumors in adults [1]. The current treatment standard is a multimodal approach combining neurosurgery, fractionated radiation therapy and chemotherapy with the DNA methylating agent temozolomide [2] [3] [6]. But despite continuous improvements in the treatment of GBM during the past decade, these tumors are still associated with a poor prognosis and rare long-term survival of the patients [4] [5] [6]. "
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    ABSTRACT: The survival of cancer patients suffering from glioblastoma multiforme is limited to just a few month even after treatment with the most advanced techniques. The indefinable borders of glioblastoma cell infiltration into the surrounding healthy tissue prevent complete surgical removal. In addition, genetic mutations, epigenetic modifications and microenvironmental heterogeneity cause resistance to radio- and chemotherapy altogether resulting in a hardly to overcome therapeutic scenario. Therefore, the development of efficient therapeutic strategies to combat these tumors requires a better knowledge of genetic and proteomic alterations as well as the infiltrative behavior of glioblastoma cells and how this can be targeted. Among many cell surface receptors, members of the integrin family are known to regulate glioblastoma cell invasion in concert with extracellular matrix degrading proteases. While preclinical and early clinical trials suggested specific integrin targeting as promising therapeutic approach, clinical trials failed to deliver improved cure rates up to now. Little is known about glioblastoma cell motility, but switches in invasion modes and adaption to specific microenvironmental cues as a consequence of treatment may maintain tumor cell resistance to therapy. Thus, understanding the molecular basis of integrin and protease function for glioblastoma cell invasion in the context of radiochemotherapy is a pressing issue and may be beneficial for the design of efficient therapeutic approaches. This review article summarizes the latest findings on integrins and extracellular matrix in glioblastoma and adds some perspective thoughts on how this knowledge might be exploited for optimized multimodal therapy approaches.
    Full-text · Article · Jul 2013 · Biochimica et Biophysica Acta
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    • "Today, treatment of GBM is primarily through tumor resection and subsequent radio- and chemotherapy, typically alkylating agents, e.g., temozolomide [7, 8]. Despite intensive efforts to improve current treatment and explore new therapeutic targets, pivotal clinical improvement has remained absent during the last decade [7, 9]. "
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    ABSTRACT: Glioblastoma multiforme (GBM) is an incurable form of brain cancer with a very poor prognosis. Because of its highly invasive nature, it is impossible to remove all tumor cells during surgical resection, making relapse inevitable. Further research into the regulatory mechanism underpinning GBM pathogenesis is therefore warranted, and over the past decade, there has been an increased focus on the functional role of microRNA (miRNA). This systematic review aims to present a comprehensive overview of all the available literature on the expression profiles and function of miRNA in GBM. Here, we have reviewed 163 papers and identified 253 upregulated, 95 downregulated, and 17 disputed miRNAs with respect to expression levels; 85 % of these miRNAs have not yet been functionally characterized. A focus in this study has been 26 interesting miRNAs involved in the mesenchymal mode of migration and invasion, demonstrating the importance of miRNAs in the context of the cellular niche. Both oncogenic and tumor-suppressive miRNAs were found to affect target genes involved in cell migration, cytoskeletal rearrangement, invasiveness, and angiogenesis. Clearly, the distinct functional properties of these miRNAs need further investigation and might hold a great potential in future molecular therapies targeting GBM. Electronic supplementary material The online version of this article (doi:10.1007/s12035-012-8349-7) contains supplementary material, which is available to authorized users.
    Full-text · Article · Oct 2012 · Molecular Neurobiology
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