Biology 202, Spring 2005
Second Web Papers
On Serendip

Tumors that are found in the brain are either classified as benign or malignant. Some of the benign tumors are pituitary adenoma and acoustic neuroma. Benign tumors are non-cancerous because they do not spread or invade surrounding tissues. These tumors, however, can be life-threatening when they are located in vital areas where they can exert pressure on nerve tissue in the brain (2). Malignant tumors, on the other hands, are glioma and metastasis like breast cancer. Malignant tumors are cancerous, and they are further classified as primary or secondary tumors. A primary brain tumor is one that originates in the brain. The tumor is named after the cell type from which it originates or the location in which the cancer develops. Secondary brain tumors are caused by cancer cells that spread to the brain from a primary cancer that is found in another area of the body. They occur more frequently than primary brain tumors. These tumors travel to the brain by blood vessel because the brain has no lymphatic drainage system (4).

Depending upon the size and the location of the tumor in the brain, the symptoms that result from the tumor are very diverse. Some of the common biological symptoms include brain edema, increased pressure in the skull, and inflammation around the tumor mass. Furthermore, the tumors can cause focal neurologic symptoms by damaging local tissue. The patients might experience difficult in speaking, hemihypoesthesai, aphasia, hemiparesis, or ataxia (3). They also suffer headaches, seizures, nausea, vomiting, vision, and hearing problems. Some of the behavioral and cognitive problems include loss of recent memory, inability to concentrate, loss of inhibitions, loss of consciousness, intellectual decline and a decrease in tolerance and patience (5).

Since most of the brain tumors are caused by damaged or missing genes that produce cells with uncontrolled growth, researchers believe that introducing a specific genetic material (DNA or RNA) into the cells will help the cells function normally again. The concept is that the incorporated genetic material will restore a missing function or provide the cells with a different set of functions. There are several ways in which researchers are using gene therapy to treat cancer cells. In one approach, researchers add healthy functioning genes to cells that have damage or missing genes in order to substitute the bad non-working copy of the gene with a better copy of the working gene (6). In other studies, scientists inject tumor cells with genes that make them more vulnerable to chemotherapy and radiation therapy. Researchers can also inject genes into cancer cells so that they can be easily detected and destroyed by the immune system or use gene therapy to increase and stimulate the body's ability to fight off cancer cells. Other research is aimed toward finding a gene that can be inserted into the cancer cell and prevent the tumor cells from forming new blood vessels (angiogenesis), so that the blood supply of the tumors will be cut off and stop the tumors from growing (6). One of the most radical treatments of gene therapy is to inject the cancer cell with genes that can destroy the cells. For instance, suicide genes are inserted into the tumor cells. A pro-drug or an inactive form of a toxic drug is administered to the patients, and this drug will kill off any cancer cells with the suicide genes in them.

In order to treat patients with gene therapy, however, it is important for the researchers to know what gene is altered or missing, and how to incorporate these new functioning genes into the cells. One method that is commonly used in lab is the in-vivo techniques. Virus or a plasmid is absolutely necessary because gene cannot be directly inserted into a cell. The gene is inserted into the person's cell by using a vector. A vector acts as a bacteriophage or a plasmid (circular, small pieces of DNA) that can transfer genes from one cell to another. Vectors from the viruses' adenoviruses are often used for gene therapy because viruses reproduce by inserting their genetic material into the cells they infect. In addition, viruses can be directed to attack specific types of tumor cells. In the lab, researchers insert the wanted gene into the virus, and inactivate or remove certain genes that can cause disease (7). The virus is injected into the patient to infect the cancer cell and the new gene will then pass on to these cancer cells.

Scientists can also transfer genetic materials into cancer cells by using ex-vivo techniques. Cancer cells are taken out of the body from the patient's blood or bone marrow, and the necessary genes are added to them in the lab (6). The cells are later placed back into the patient by injection into a vein. This process is used to get the body's immune system to attack the cancer cells that look like the new incorporate cells in the body by making the cancer cell more easily detected by the immune system. On the other hand, immune cells (dendritic cells) can also be removed from the body and altered to make them stronger and more likely to go after cancer cells once they are placed back into the body (7).

Gene therapy, thus, has some potential toward treating brain cancer, but scientists are still very skeptical about it because they have discovered many risks and flaws with the treatment. First of all, gene therapy is not suitable for all patients with brain tumors, and it is not guaranteed to work for all types of brain cancer. Thus, patients who show an interest in gene therapy must undergo a rigorous screening process to determine their eligibility. Some screenings include the Karnofsky assessment, a neurologic examination, as well as physical examinations to test overall health. Patients who are qualified for this treatment are those that have recurrent malignant gliomas or who have just been diagnosed with malignant gliomas (8). Furthermore, their tumors must also be accessible by surgery and have proven not to respond well to standard treatments like mediation and radiation. Gene therapy should only be considered as a possible treatment for people who are suffering from malignant tumors such as glioblastoma mutliforme, and only for cases in which all conventional therapies have failed.

There are also many risks that are associated with gene therapy and many feel that gene therapy is still lacking in its ability to fight brain tumors. In order to inject gene cells into the specific region of the brain, doctors are required to performed stereotactic brain surgery. Some risks from the surgery might include hemorrhaging or deterioration of functions in the nervous system. After the genes are injected into the region, there is the possibility that the viral vectors that are used to transfer the genetic material into the cell might infect healthy cells as well as cancer cells (9). The new gene might also insert into the wrong location in the DNA, thus leading to harmful mutations of the DNA and triggering unwanted reaction by the immune system. The transferred genes can also be overexpressed by producing a lot of missing proteins. Finally, inflammation of the lining of the brain or infection can occur after the treatment (8).

One of the biggest problem facing gene therapy is the possibility that if this treatment is effective in curing brain tumors, people will allow scientists to use gene therapy to target germ cells and let the inserted gene be passed on to the future generation. The positive side of this germline gene therapy is that future generations in the family with this genetic disease (brain tumor) can be saved from it (7). The negative side, on the other hand, is that the gene therapy will affect the development of the fetus in many unexpected ways like causing long-term illness or other side effects. The human gene pool can also be permanently affected by these gene alterations.

With all the risks and ethical issues that are involved with gene therapy, this treatment is only currently available in research settings. As a result, there is a very slim chance that gene therapy can become a common technique for treating brain tumors. However, if researchers are able to overcome some of the problems that result from gene therapy, there is still a possibility that it can be used to help save million of people that are suffering from cancer. For instance, scientists should find more efficient ways to inject genes into the cell, like creating vectors that specifically focus on the target cells. Researchers can also try to manipulate and control the body's physiologic signals and pathway in order to achieve a greater precision of transplanting the genes to specific locations in the patient's DNA. Even though there is a huge risk with gene therapy, one must be willing to take that risk to survive.

WWW Sources

1)Cancer Facts and Figures 2005, Publication summarize the current scientific information about cancer in 2005

2) Brain and Spinal Cord Tumors in Adults, A description to the causes, symptoms, and treatments for brain tumors.

3)Brain Tumors: Primary, A publication about primary brain tumors in 2001.

4)Brain Tumors, A free encyclopedia (Wikipedia) that has article on brain tumor.

5)Clinical Trials and Noteworthy Treatments for Brain Tumors, This website main focus is toward brain tumor symptoms.

6)Making Treatment Decisions, This article talks about gene therapy treatment.

7)Cancer Facts, Gene Therapy for Cancers: Questions and Answers.

8)National Brain Tumor Foundation, Gene Therapy: A New Experimental Treatment for Brain Tumors

9)Gene therapy of brain tumors: problems presented by physiological barriers, The article is about gene having problem crossing the blood brain barrier.


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