Adrenomedullin and Nitric Oxide: Implications for the Etiology and Treatment of Primary Brain Tumors

Ana      P. Fernandez; Julia      Serrano; Miguel      A. Amorim; Andrea      Pozo-Rodrigalvarez; Ricardo      Martinez-Murillo

Abstract

Gliomas, defined as tumors of glial origin, represent between 2-5% of all adult cancer and comprise the majority of primary brain tumors. Infiltrating gliomas, with an incidence of more than 40% of brain tumors, are the most common and destructive primary brain tumors for which conventional therapies have not significantly improved patient outcome. In fact, patients suffering from malignant gliomas have poor prognoses and the majority have local tumor recurrence after treatment. Tumor growth and spread of tumor cells depend basically upon angiogenesis and on functional abnormalities of tumor cells in the control of apoptosis, as they are paradigmatic for their intrinsic resistance to multiple pro-apoptotic stimuli. Therefore, promising strategies for treatment of brain cancer would be directed to appropriate neutralization of angiogenesis and sensibilization of cancer cells to undergo apoptosis. However, despite advances in this field, high-grade gliomas remain incurable with survival often measured in months. Therefore there is a need to discover new and more potent cocktails of drugs to target the key molecular pathways involved in glioma angiogenesis and apoptosis. This review deals with the effects of two groups of molecules closely linked to neural tissue, which have been implicated in brain cancer: nitric oxide and peptides of the adrenomedullin family. These molecules exert vasodilatory and proangiogenic actions. Adrenomedullin also has antiapoptotic functions at appropriate concentrations. The inhibition of these functions, in the case of cancer, may provide new pharmacological strategies in the treatment of this disease.

Keywords: Adrenomedullin, angiogenesis, Antiangiogenic treatment, Apoptosis, Astrocytoma, Brain tumor, Glioma, Nitric Oxide, Bevacizumab, PAMP, GBM