Research Efforts

In the past we have conceived of brain tumors as a mass of abnormal tissue within the good tissue of the brain. This mass can be removed by surgical techniques which have evolved over the past 100 years. Brain tumor surgery is now more effective and safer than ever before. Our surgical techniques now employ state-of-the-art technology ; LASERS, computers and advanced imaging techniques such as magnetic resonance imaging (MRI), and positron emission tomography (PET). Nonetheless, we cure very few glioblastomas, astrocytomas, mixed gliomas and oligodendrogliomas. By the time the diagnosis is made most of them have infiltrated into surrounding brain tissue which cannot be removed without devastating the patient. These residual cells continue to grow and result in a "recurrance" of the tumor.

Our understanding of them has been far too simplistic. Gliomas are much more complicated than a simple mass that can be excised. Brain tumors, like tumors in any organ system, are composed of millions of individual cells which co-exist within the normal tissue. These cells, tumor cells and normal cells, form a complex ecosystem. Each cell can function independently: they breathe, they move, they excrete waste and they reproduce through a process of mitosis.

Mitosis is the process by which one cell splits and becomes two cells. When mitosis occurs at an abnormally high rate in cells within an organ system, such as the brain, a tumor results. Sometimes the cells pile up one upon the other and displace the normal tissue. Sometimes, they invade as individuals into the normal brain tissue and happily coexist with the cells that should be there.

Tumor cells are not like the normal cells that make up the brain. They look different and act differently. Tumor cells lack the specialized function that the astrocytes, oligodendroglial cells and neurons possess; the functions that make normal cells useful to the organ as a whole Tumor cells are different because something in their genetic structure, their DNA, makes them different.

We are now on the verge of mapping the entire human genome: the complicated sequence of DNA specific to the human animal. DNA - the gene - is the master controller of all cell processes. There is already a wealth of information about genetic abnormalities in tumor cells. With this knowledge will be able to discover how and why tumor cells are different from normal cells. We will determine what makes them divide and move when normal cells stay put.

All cells-normal and abnormal- have a self destruct mechanism. This is also controlled by a genetic program. This process, called apoptosis, is the explanation of why some tumors such as subependymomas which have a high rate of mitosis but grow very slowly, if at all. They have a high rate of mitosis but also a high rate of apoptosis. Cells being born are offset by cells which are dying and the population of cells in the tumor stays the same. If we could increase this rate of apoptosis in all tumors we could control their growth. Again this control mechanism is orchestrated by the DNA.

The goal of genetic therapies in tumors is to change or replace the abnormal DNA of tumor cells. This will enable us to control them or selectively destroy them. In addition, with knowledge of the genome we will learn how normal cells evolve into the specialized single celled animals that they are. And we will learn what makes normal cells turn into tumor cells and what internal mechanisms control their growth rate.

Using molecular therapeutic methods we may be able to convert cells of one type into cells of another type by transforming or replacing their DNA. For example, we may be able to transform fibroblasts, the cells that form simple scar tissue, or other cell types into neurons that will repopulate brain areas destroyed by strokes, injuries or degenerative diseases such as Alzheimer's. We may be able to produce new oligodendroglial cells, the cells that form myelin, the substance which is damaged in multiple sclerosis. These can be used to repair the damage and restore victims of demyelinating disease to useful function. And we may be able to convert tumor cells back into normal cells by replacing their DNA.

New DNA can be inserted into tumor cells by means of a sub-microscopic viral vector. This means a genetically engineered virus that will "infect" tumor cells, destroy the DNA and replace it with normal DNA.Sound impossible? Viruses, have been doing this to cells of various organisms for billions of years!

Viruses are the simplest of lifeforms. They consist of a shell of protein which holds a nucleic acid - like DNA. Viruses attach themselves to cells and replace the cell's DNA with their own. We can now engineer viruses in the laboratory which have normal human glial DNA.

As we learn more about the inner workings of brain tumor cells we are discovering many other fascinating things. For example, these simple single celled animals actually talk to each other. They also talk to the normal cells around them. They talk not with words but with chemical messengers called cytokines. A group of tumor cells can send a message to a normal blood vessel which causes the endothelial cells in the blood vessel to grow toward the group of tumor cells and supply them with the oxygen and glucose they need to live and to grow. The endothelial cells send messages to the tumor cells saying "grow this way". Understanding these so-called growth factors will provide future methods by which doctors can manipulate the behavior of tumor cells and ultimately cure tumors.