Glioblastoma multiforme: A brief on current and new treatments.

Glioblastoma multiforme (GBM) is a widely recognized brain tumor, and it represents up to half of all the primary brain glioma. It accounts for up to 15% of all brain tumors. Genetic events and signaling pathways have shown GBM to be an anaplastic and morphologically heterogeneous tumor. Knowledge of change in genetics, molecular biomarkers, and proliferative pathways can lead to an improvement in the treatment of GBM. Histology, position, and tumor resection are recognized as potential prognostic elements for patients of GBM. 

At a molecular level, there are two types of necrosis associated with GBM. The first one results from insufficient blood supply in primary glioblastomas, characterized by necrosis inside the focal range of the tumor, and the latter one by pseudo palisading zones produced by a radial arrangement of glial cells observed in primary and secondary glioblastoma (1). Microvascular hyperplasia and zone of necrosis surrounded by pseudo palisades which facilitate the growth of the tumor along with its characterization at tissue level are key parameters for the conclusion of GBM (2,3).

Current treatment

Combination therapy of radiation and temozolomide before adjuvant therapy is reported to be an effective way of treating patients. Another procedure is interstitial brachytherapy which makes use of catheters placed in tissues to administer Iodine-125 radioactive seeds for treatment which can result in improved median survival of patients (4).

New therapy

The current standard way of treatment does not enhance the survival of patients and thus there is a need for novel treatment. Improved abnormalities of blood vessels can alter the micro-environment and enhance the efficiency of anti-cancer agents. Angiogenesis inhibitors are under study (5). Abergrin is an antibody that can inhibit avβ3 integrin and prevent endothelial migration and adhesion to form new unwanted vascular structures (6). Tyrosine kinase and VEGF inhibitors can also stop the formation of abnormal vascular structure and reduce edema, respectively (7,8). Another method is the use of Cannabinoids found in cannabis, it can inhibit angiogenesis and induce apoptosis in tumor cells (9). 

Conclusion

The capability of invading normal brain tissues and poor survival of the affected patients are a few of the characteristics of GBM. Current treatment strategies are not effective enough and do not show any significant increase in survival rate. New treatment strategies that can target tumor cells efficiently and enhance a patient’s survival are explorative. It requires an organized study on these novel agents to improve a patient’s survival.

References

1.Kleihues P, Burger PC, Collins VP, Cavenee WK. Pathology and genetics of tumors of the nervous system. IARC Press, Lyon 2000.

2. Steck PA, Lin H, Langford LA, et al. Functional and molecular analyses of 10q deletions in human gliomas. Genes Chromosomes Cancer. 1996;24:135–143. 

3. Brat DJ, van Meir EG. Vaso-occlusive and prothrombotic mechanisms associated with tumor hypoxia, necrosis, and accelerated growth in glioblastoma. Lab Invest.2004;84:397–405.

4. McDermott MW, Sneed PK, Gutin PH. Interstitial brachytherapy for malignant brain tumors. Semin Surg Oncol. 1998;14:79–87. 

5. Chi AS, Sorensen AG, Jain RK, Batchelor TT. Angiogenesis as a therapeutic target in malignant Gliomas. Oncologist. 2009;14:621–636. 

6. W. Cai, Y. Wu, K. Chen, Q. Cao, D. A. Tice, and X. Chen, “In vitro and in vivo characterization of 64Cu-labeled Abegrin™, a humanized monoclonal antibody against integrin αvβ3,” Cancer Research, vol. 66, no. 19, pp. 9673–9681, 2006. 

7. W. Fiedler, R. Mesters, M. Heuser et al., “An open-label, Phase I study of cediranib (RECENTIN™) in patients with acute myeloid Leukemia,” Leukemia Research, vol. 34, no. 2, pp. 196–202, 2010. 

8. Moustakas A, Kreisl TN. New treatment options in the management of glioblastoma multiforme: a focus on bevacizumab. Oncol Targets Ther. 2010;3:27–38. 

9. Blazquez, C., Salazar, M., Carracedo, A., Lorente, M., Egia, A., Gonzalez-Feria, L., . . . Guzman, M. (2008). Cannabinoids Inhibit Glioma Cell Invasion by Down-regulating Matrix Metalloproteinase-2 Expression. Cancer Research, 68(6), 1945-1952. doi:10.1158/0008-5472.can-07-5176.