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Cancer is caused by changes in our genes. In recent years,
researchers have learned a great deal about how these gene changes can
lead to cancer. Gene therapy may be a way to overcome these changes in
order to treat or even prevent cancer.
Although it holds great hope for the future, for now, gene
therapy is limited by our technical abilities. It will probably be
years before gene therapy is available to cancer patients other than in
research studies.
What is a gene?
Our bodies are made up of a complex mix of chemicals. Most
important body functions use chemicals called proteins. Each
protein has a specific function. For example, some proteins help cells
in the body to keep their shape, while others allow them to grow and
divide normally.
Genes are the "blueprints" for making proteins. Each cell in
the body has a complete set of these blueprints. Genes are made of a
substance called DNA,
which stands for deoxyribonucleic acid. DNA sits in long double strands
called chromosomes
in the middle (nucleus) of each cell. RNA (ribonucleic acid) is a
single strand of DNA. It is used to carry the information from the DNA
genetic code to areas in the cells that make proteins.
Our genes are passed on to us (inherited) from our parents.
Genes are responsible for many of the traits we can easily see, such as
the color of our eyes and whether or not we have curly hair. But genes
can have other effects too, such as on our tendency to get diseases
like cancer.
Sometimes changes (mutations) in genes are inherited from our
parents. But more often, genes change during our lifetime, such as when
a cell is exposed to something that damages its DNA, such as radiation,
the sun, or cigarette smoke. These gene changes, in turn, affect the
proteins they make. If a protein is normally involved in keeping the
cell's growth in check, a damaged gene making a faulty protein may lead
to unwanted cell growth.
Researchers now believe that for most cancers to develop, it
probably requires changes in several of our genes. These changes can
either be inherited from our parents or acquired during our lives.
To learn more about genes and how they relate to cancer, see
our document Oncogenes
and Tumor Suppressor Genes.
What is gene therapy?
Gene therapy is treatment to correct faulty genes that cause
diseases to develop. Genetic material (DNA or RNA) is inserted into
cells to restore a missing function or to give the cells a new
function. Because missing or damaged genes cause certain diseases such
as cancer, it makes sense to try to treat these diseases by adding the
missing gene(s) or fixing those that are damaged. But it has not been
easy to figure out how to do this.
Gene therapy for treating inherited genetic
diseases
Scientists think gene therapy may be best suited for treating
inherited disorders caused by single gene defects, such as cystic
fibrosis, hemophilia, sickle cell disease, and severe combined
immunodeficiency. In fact, gene therapy has already been used to treat
some children with severe combined immunodeficiency disorder (SCID), a
rare and often deadly disease in which the immune system doesn't work
the way it should. Gene therapy has restored the immune systems of more
than a dozen children with SCID. But there have also been some
complications from this treatment: a few of the children have developed
leukemia as a result of therapy. Unforeseen problems like this have
caused researchers to temper their enthusiasm and be more cautious with
further studies.
Gene therapy and cancer
Scientists have learned that cancer is the result of gene
mutations. As a result, they have come to think that gene therapy may
be a way to treat cancer. Cancer is much more common than inherited
genetic disorders. Because of this, interest in research into cancer
gene therapy has grown in recent years. In fact, most gene therapy
clinical trials done today are related to cancer.
Gene therapy may some day be used against cancer in many
different ways. Scientists are trying to use gene therapy by:
- Adding
healthy genes to cells that have abnormal or missing genes.
For example, cells normally have tumor
suppressor genes such as p53 that help prevent cancer from
developing. But many cancer cells have faulty p53 genes. We may be able
to bring these cancer cells back under control by placing a working
copy of the p53 gene into them.
- Stopping
oncogenes (or other genes important to cancer) from working.
Oncogenes
are mutated forms of normal genes that cause cells to divide out of
control, leading to cancer. Other genes are important in allowing
cancer cells to metastasize (spread to other parts of the body).
Stopping these genes or the proteins they make may prevent cancer from
growing or spreading.
- Adding or
changing genes to make cancer cells more unstable. Cancer
cells often have changes in genes that would normally repair faulty
DNA. This lack of DNA repair may allow them to grow and divide at a
rapid rate. But researchers may be able to exploit this difference
between normal and cancer cells. They may be able to add or change
faulty genes that normal cells can repair, but that cancer cells
cannot. This would lead to cancer cell death.
- Adding or
changing cancer cell genes to make them more vulnerable to cancer
treatments. Many cancer cells are resistant to
chemotherapy or radiation therapy, or they become resistant over time.
For example, some genes may help cancer cells to pump chemo drugs out
of them without causing any damage. Blocking these genes could make
chemotherapy effective against these cells.
- Making tumor
cells more easily detected and destroyed by the body's immune system.
The immune system is thought to play a role in keeping some cancers in
check. But cancer cells often find ways to elude the immune system,
allowing them to grow out of control. Gene therapy might be helpful in
2 ways. By adding the right gene to cancer cells, doctors could 'tag'
them so the immune system would then recognize and destroy them. A
closely related idea is to add genes to the right immune system cells
to make them better able to detect the cancer cells. This method has
already yielded some promising early results.
- Stopping
genes that play a role in new blood vessel formation (angiogenesis) or
adding genes that stop it. Tumors need a constant blood
supply to grow. If this supply can be cut off, tumors may stop growing
or even shrink.
How is gene therapy done?
As researchers find new genes involved in the development of
cancer, the possibilities for gene therapy continue to grow. Of course,
in order to treat someone with gene therapy, doctors have to know which
genes are altered or missing. While our knowledge of gene mutations
involved in cancer continues to grow, our ability to detect these
changes in individuals is still fairly basic. But research in this area
continues at a rapid pace.
Cells used in gene therapy
Researchers have focused on 2 major targets in cancer gene
therapy: the tumor cells themselves and immune system cells that might
be induced to attack the tumors.
Tumor cells
Tumor cells are the obvious target for gene therapy. Using
either in vivo ( in the body) or ex vivo (outside the body) techniques,
gene therapy is being studied as a way to cause tumor cells to die, or
at least stop growing rapidly( see the next section for a description)
. It may also be used to add genes to make the cells more visible to
the immune system or more sensitive to chemotherapy, radiation therapy,
or other treatments.
Immune system cells
Some immune system cells may be useful in gene therapy. For
example, special immune cells called dendritic cells
seem to be very important in helping the immune system to attack
cancer. They can be removed from the body and then altered in the lab
to make them more likely to attack cancer cells once they are put back
into the body. Studies involving dendritic cell cancer "vaccines" are
among the furthest along in terms of gene therapy development.
Techniques for getting genes into cells
So far, the biggest obstacle to gene therapy has been the
ability to get genes into the target cells. There are 2 main techniques
(in vivo
and ex vivo)
for doing this.
In vivo techniques
One approach is to somehow put copies of the gene into the
body, where they will be taken up by the cells you want to target.
These are known as in vivo (within the body) techniques. One of the
concerns with these techniques is that the genes may have to be put
right into the tumor(s) to have an effect. This could be a problem for
hard to reach tumors or in patients whose cancer may have already
spread to many different parts of the body.
Ex vivo techniques
Another approach is to take some of the targeted cells out of
the body, add the needed gene(s) to them in the lab, and then put them
back into the body. This is known as an ex vivo (outside of the body)
approach.
This is more likely to be useful for activating the immune
system to fight the cancer. For example, immune system cells might be
removed from the blood or bone marrow, given genes in the lab to help
them find and kill the cancer cells, and then put back into the
patient. Or cancer cells could be removed by surgery, treated in the
lab to make them more likely to provoke an immune response, and then
put back into the body. The immune system would then attack these
cancer cells and other cells like them in the body.
Vectors (carriers) to get genes into target
cells
Genes, which are small strands of DNA, are not easily inserted
into cells. Just injecting many copies of a gene into the body (such as
into the bloodstream) isn't likely to be helpful, because the DNA would
be destroyed before it ever got into the cells.
Researchers are studying different types of vectors that can
be used to help get genes into the target cells.
Viruses
We normally think of viruses as germs that cause infections.
But viruses have some special properties that make them useful tools in
gene therapy. Viruses reproduce by "hijacking" infected cells.They
inject their genes (in the form of DNA or RNA) into the cells they
infect, which causes the cells to make the protein parts for more
viruses. Many viruses attack only certain kinds of cells, which means
it might be possible to direct them at specific types of tumors.
Gene therapy researchers try to use only viruses that might be
well-suited for the task. They use viruses that are fairly stable and
aren't likely to cause disease. In the lab, the needed gene is put into
the virus, and any harmful viral genes are removed. The virus is then
given to the patient (via either an in vivo or ex vivo technique)
to "infect" the cancer cells, and the gene is passed on to these cells.
At this time, viruses seem to be the best vector for getting genes into
cells.
But there are some possible problems using viruses in gene
therapy. Viruses may trigger an unwanted reaction by the body's immune
system, which could make the treatment ineffective (especially after
the first round of therapy) or even lead to more serious health
problems such as autoimmune reactions. Another concern is that
researchers can't always control exactly where the viral gene might be
inserted into the cell's DNA. It could possibly insert itself into the
middle of one of the cell's functioning genes, leading to an unwanted
mutation.
Liposomes
Another strategy is to try to put a copy of the gene into the
cells using liposomes, which are tiny fat bubbles. In the lab, the
bubbles are created around plasmids,
which are small, circular pieces of DNA. Once injected into the body,
the liposomes can join with cell membranes, emptying their plasmid DNA
contents into the cells.
Using liposomes as a vector has some advantages and
disadvantages when compared to using viruses.
This method is less likely to provoke an immune response and
may cut down on the chances that the patient will become sick from the
treatment. Liposomes can also hold larger amounts of DNA than viruses,
which means they may be better suited for carrying larger genes.
Finally, liposomes can be modified by changing the contents of the
fats, proteins, or other molecules that make up the bubble. This may be
helpful in targeting them at specific types of cells in the body.
But liposomes may not work as well as viruses because the DNA
is less likely to end up inside the cells. And because the liposome-DNA
complex has to be injected right into the tumor itself, there may be
limits as to what kinds of cancers it can be used for.
Related forms of therapy
Other gene-based forms of therapy are also under study.
Instead of directly affecting the genes themselves, these approaches
affect the cells' ability to turn genes into proteins. They work by
attacking messenger RNA (mRNA), which is the intermediate step between
a gene and its protein.
For example, scientists are now trying to use mirror images of
faulty genetic material (called antisense DNA or RNA). These substances
bind to specific mRNAs, which stops the gene from making its protein.
A newly discovered type of RNA (known as small interfering RNA,
or siRNA), may also be useful in preventing genes from being turned
into proteins.
Again, the main problem with these approaches may be getting
these small molecules into the target cells. Research in this area is
under way.
When will gene therapy be available?
Although gene therapy has been successful in treating some
genetic diseases, it is currently available as cancer treatment only
through clinical trials. It will probably be many years before gene
therapy is ready for use to the general public.
Many studies of gene therapy are being done to treat different
kinds of cancer. Some of these are using gene therapy alone, while
others are using it along with more traditional treatments such as
radiation or chemotherapy.
In 2006, the first successful use of gene therapy to treat
cancer was reported. Researchers removed immune system cells called
T-lymphocytes from the blood of 15 patients with advanced melanoma. In
the lab, they used a virus to add a new gene to these cells, which
enabled the cells to recognize and attack cancer cells. They then
injected these cells back into the patients. More than a year after
treatment, 2 of the 15 patients had their tumors shrink to the point
that they were no longer detectable. While this small study showed that
gene therapy can be helpful against cancer, it will still be some time
before the technique is improved upon enough to be more widely useful.
There is little doubt that the techniques used in gene therapy
will continue to improve. As they do, it is likely that gene therapy
will one day become an important way to treat cancer.
Additional resources
More information from your American Cancer
Society
The following information may also be helpful to you. These
materials may be viewed on our Web site or ordered from our toll-free
number.
National organizations and Web sites*
Along with the American Cancer Society, other sources of
information and support include:
National Cancer
Institute
Toll-free number: 1-800-4-CANCER (1-800-422-6237)
Web site: www.cancer.gov
Provides accurate, up-to-date information about cancer for patients,
their families, and the general public. Also provides comprehensive
clinical trials information on understanding trials, deciding whether
to participate in trials, finding specific trials, plus research news,
and other resources.
*Inclusion on
this list does not imply endorsement by the American Cancer Society.
No matter who you are, we can help. Contact us anytime, day or
night, for cancer-related information and support. Call us at 1-800-227-2345 or
visit www.cancer.org.
References
American Society of Gene Therapy. Information about Gene
Therapy. Accessed at: www.asgt.org/about_gene_therapy/diseases.php on
June 5, 2009.
Human Genome Project Information. Gene Therapy. Accessed at:
www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml
on June 5, 2009.
Morgan RA. Gene therapy. In: DeVita VT, Lawrence TS, Rosenberg
SA, eds. Cancer:
Principles & Practice of Oncology. 8th ed.
Philadelphia, Pa. Wolters Kluwer/Lippincott Williams & Wilkins;
2008: 2967–2978.
Morgan RA, Dudley ME, Wunderlich JR, et al. Cancer regression
in patients mediated by transfer of genetically engineered lymphocytes.
Science.
2006;314: 126–129.
National Cancer Institute. Gene Therapy for Cancer: Questions
and Answers. Accessed at:
www.cancer.gov/cancertopics/factsheet/Therapy/gene on June 5, 2009.
Stein CA, Benimetskaya L, Kornblum NS, Mani S. Antisense
agents. In: DeVita VT, Lawrence TS, Rosenberg SA, eds. Cancer: Principles &
Practice of Oncology. 8th ed. Philadelphia, Pa. Wolters
Kluwer/Lippincott Williams & Wilkins; 2008: 522–527.
Talmage JE, Cowan KH. Gene therapy in oncology. In: Abeloff
MD, Armitage JO, Niederhuber JE, Kastan MB, McKenna WG, eds. Clinical Oncology.
3rd ed. Philadelphia, Pa. Elsevier; 2004: 603–622.
Last Medical Review: 07/08/2009
Last Revised: 07/08/2009
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