- Oncogenes, Tumor Suppressor Genes, and Cancer
- How do cells know what to do?
- What are mutations?
- Gene mutations that can lead to cancer
- How can oncogenes and tumor suppressor genes be used to help prevent cancer?
- How can oncogenes and tumor suppressor genes be used to help guide treatment of cancer?
How can oncogenes and tumor suppressor genes be used to help guide treatment of cancer?
In some cases, specific gene changes help predict which patients are likely to have a better or worse outlook or which patients are likely to benefit from certain treatments.
For example, HER2/neu is a proto-oncogene present in normal cells. It becomes an oncogene when a cell has too many copies of this gene. When this happens, the cells make too much HER2/neu protein. Many years ago, experts realized that patients with breast cancer with cells that have too much HER2/neu protein had a worse outcome than patients whose cancer cells have normal amounts. Cancers with too much of this protein did not respond as well to certain chemotherapy drugs, so now other drugs are used. Drugs were also designed to specifically attack cells with too much HER2/neu (these are discussed below). Treatment with these drugs have also helped improve outcomes for these patients.
Some tests for certain gene mutations are very sensitive in finding cancer that persists or returns after treatment. For example, the leukemia cells of patients with chronic myeloid leukemia (CML) contain a mutated gene called BCR-ABL. Testing for this mutation is used to confirm the diagnosis of CML and then to see if treatment is working. This testing can also be used to see if the leukemia has started coming back after treatment. Instead of having to look for abnormal cells in the bone marrow, a blood test for the abnormal gene can find even small numbers of remaining cancer cells among millions of normal cells. This may signal that new treatment is needed. The BCR-ABL gene is also important in the treatment of CML. This is discussed below.
How can oncogenes and tumor suppressor genes be used to treat cancer?
The discovery and understanding of oncogenes and tumor suppressor genes has led to the development of new kinds of cancer therapies. The following are some examples of genes that are cancer treatment targets. Research in this area is progressing rapidly, and new drugs targeting certain genes and proteins are becoming available over time.
In some cases of breast cancer, the cells have too many copies of a gene called HER2/neu and make an excess amount of the HER2/neu protein. This protein promotes the growth of cancer cells. But drugs have been developed that target this protein, slowing cancer cell growth and improving outcomes. These drugs, trastuzumab (Herceptin®) and lapatinib (Tykerb®), only work against cancers that have too much HER2/neu (called HER2-positive). Breast cancers are now routinely tested for the HER2/neu gene and/or protein to identify which patients will benefit from these drugs. Trastuzumab has also been shown to be useful in treating people with stomach cancer that is HER2-positive. Other drugs targeting HER2 are being tested in clinical trials.
In chronic myeloid leukemia (CML), the cancer cells have a gene change called BCR-ABL that makes a type of protein called a tyrosine kinase. Drugs that target the BCR-ABL protein, including imatinib (Gleevec®), dasatinib (Sprycel®), and nilotinib (Tasigna®), are often very effective against CML. They lead to remission of the leukemia in most patients treated in the early stages of their disease. Other drugs to target the BCR-ABL protein are being studied for use if these drugs stop working.
Most gastrointestinal stromal tumors (GISTs) are caused by activation of the oncogene called KIT. Others are caused by activation of PDGFRA, another oncogene. The drug imatinib (Gleevec) targets both of these oncogenes, and is often able to shrink these tumors and help patients live longer. Sunitinib (Sutent®) is also able to target these oncogenes and can be helpful if imatinib no longer works.
Tumor suppressor genes
Treating problems in tumor suppressor genes is more difficult. It would mean restoring normal tumor suppressor gene functions, which researchers have not yet figured out how to do effectively. A major stumbling block lies in how to get new DNA into the cancer cells. Another problem is that most cancers have several mutations, so replacing one gene may not be enough to stop the cancer cells from growing and spreading.
Scientists tried to treat some cancers that have mutations in the TP53 gene by inserting normal TP53 genes into viruses and then trying to infect tumor cells with these viruses. This worked well in the lab, but not in human studies.
A newer approach targets the weakness in the cell caused by the abnormal tumor suppressor genes, rather than trying to restore normal gene function. For example, some people inherit a mutation in one of the BRCA genes (BRCA1 or BRCA2). If the second copy of this gene is damaged, the gene no longer works and they may develop a cancer. In cells where a BRCA gene no longer works (like cancer cells), drugs called PARP inhibitors cause DNA damage that can lead to cell death. Cells that have normally functioning BRCA genes can repair this damage. This allows the PARP inhibitor to target the cancer cells while doing little damage to the normal cells.
Many researchers are very hopeful about the future of cancer therapies using oncogenes and tumor suppressor genes, and this remains a very active area of research. There are many clinical trials under way today that could lead to better treatments for many types of cancer.
To learn more
More information from your American Cancer Society
We have some related information that may also be helpful to you. These materials may be viewed on our Web site or ordered from our toll-free number, at 1-800-227-2345.
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 on a variety of cancer-related topics such as finding support, financial assistance and other resources; coping with cancer; cancer genetics, etc. (click the “Cancer Topics” tab on the home page). Also has an Online Cancer Genetics Services Directory to identify professionals who provide services related to cancer genetics (cancer risk assessment, genetic counseling, genetic susceptibility testing, and others). The direct link is www.cancer.gov/search/geneticsservices.
National Society of Genetic Counselors (NSGC)
Web site: www.nsgc.org
Offers a Consumer Information link with the following:
- Making Sense of Your Genes: a 24-page guide to genetic counseling (may be downloaded and printed)
- Directory of genetic counselors: can be searched by your area
- Five Questions to Ask Before Considering Genetic Testing (can be downloaded and printed)
- Guide on collecting family history: a helpful tool in determining possible genetic risks
- FAQs on genetic testing and genetic counselors
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.
Last Medical Review: 12/27/2011
Last Revised: 12/27/2011