Novel Gene Therapeutic Approaches to Brain Cancer

INTRODUCTION In the United States, approximately 17,000 people per year are diagnosed with brain tumors, the leading cause of death from cancers in children ages 1-15 year (1,2). Gliomas are the most prevalent type of brain tumors in adults, affecting 3.2/100,000 persons/yr in the United States (www.CBTRUS.org). In spite of advances in surgery, chemotherapy, and radiotherapy, the mean survival time of patients post-diagnosis remains approximately 9-12 months. The nervous system is comprised of neurons supported and nourished by glial cells. There are four different types of glial cells: astrocytes, oligodendroctyes, microglia, and ependymal cells. Technically, a glioma is defined as "any neoplasm [an uncontrolled growth of abnormal tissue] derived from one of the various types of cells that form the interstitial tissue [glial cells] of the brain, spinal cord, pineal gland, posterior pituitary gland, and retina"(3), and they can also be found in nasal lobes, peripheral, and cranial nerves. In general, gliomas rarely metastasize beyond the central nervous system (CNS); however, tumors from other parts of the body can metastasize to the CNS. Gliomas may be found in many different regions of the CNS and are usually comprised of a heterogenous cellular population. There are many different types of gliomas each with its own characteristic features. For example, there are brainstem gliomas, gigantocellular gliomas, mixed gliomas, nasal gliomas, gliomas of the optic chasm, optic nerve gliomas, gliomas of the spinal cord, telangiectactic gliomas (4). However, we will only discuss the main types: astrocytomas and mixed gliomas. Astrocytomas are located anywhere in the CNS, grow slowly, are invasive and are believed to originate from astrocytes. The most devastating type of astrocytoma, grade-four astrocytoma, is more commonly known as glioblastoma multiforme. It is located mostly in the cerebral hemisphere, is highly invasive, 230 Castro et al. malignant, and probably originates from mature astrocytes. Glioblastomas are the most cornmon type of brain tumors diagnosed in middle aged adults, accounting for about 30% of all primary brain tumors. They are the most malignant of all brain tumors and the most difficult to treat with mean survival of less than 1 year following diagnosis (4). Astrocytoma is also the most cornmon pediatric tumor diagnosed, accounting for just over 50% of all newly diagnosed tumors in children (5). The diagnosis of gliomas includes recognition of its symptoms, performing physical tests and assigning a grade to the tumor. Symptoms of gliomas can include headaches (where pain increases …