Exciting, new gene therapy treatments for breast cancer are on the verge of making a breakthrough. With proper funding, these procedures could reduce the need for the surgical removal of organs.
By Rayan Kaakati, Neurobiology, Physiology, and Behavior
Being born female automatically enters one in a game of Russian roulette: About 1 in 8 women will develop invasive breast cancer over the course of their lifetime; for American women, breast cancer is the second leading cause of death (U.S. Breast Cancer Statistics).
Breast cancer is a disease that starts in the tissues of the breast and is statistically fatal for one in thirty-two women (Breast Cancer Facts). Many women, throughout recorded history, have succumbed to this malignant disease. Rapid advancements in research have been very promising for cancer cell-targeting medications and for gene modification techniques.
Medicine in the twenty-first century is still resorting to what the ancient Chinese and Arab doctors used to practice: “If cancerous, cut it out if possible,” or in current-day terms, order a “lumpectomy” or a “mastectomy” (if the entire breast is to be removed). In recent years, a toxic chemo “smoothie” and an intensive radiation regimen have been added, coupled with hormone therapy. While these medical procedures are credited with saving thousands of lives, they are still primitive compared to current, promising research works.
Around 5-10% of breast cancers arise from inherited gene mutations. Examples of mutated genes that increase one’s risk of developing breast cancer are the BRCA genes. These genes normally produce tumor-suppressing proteins to repair damaged DNA, thus preventing tumor formation. When BRCA genes are mutated, DNA damage accumulates, which increases a woman’s risk of developing the disease. Women with a BRCA1 mutation have a 55-65% risk of developing breast cancer while this risk is 45% in women with a BRCA2 mutation (BRCA1 & BRCA2: Cancer Risk & Genetic Testing). The statistic that around 5-10% of breast cancers arise from inherited gene mutations could be misleading however, as around 85% of breast cancers develop in females who have no family members with the disease (U.S. Breast Cancer Statistics). Nonetheless, the cause of the disease is still due to genetic mutations. These women have spontaneous mutations that have arisen due to the aging process—and other known and unknown causes— and thus have accumulated a number of mutations over time (Privalsky).
Recently, stories have emerged on Angelina Jolie’s “prophylactic” or risk-reducing surgery (double mastectomy) performed after she was screened and found to have inherited the defective BRCA genes from her mother, who died from breast cancer. Jolie has been a positive influence on many women, as there has been an increase in the number of women screened for the defective BRCA genes (Privalsky). Another preventative measure for those who have tested positive in a BRCA mutation involves removing a woman’s ovaries, in order to reduce the amount of estrogen circulating in the body. However, less invasive measures are needed, as many women with increased heredity risks are making the difficult decision of undergoing a mastectomy or an oophorectomy to prevent the disease.
With the appropriate amount of funding, a radical, new technique called “amino acid replacement therapy” to repair and genetically alter the BRCA genes could prove successful. The basic idea behind the treatment is to alter the amino acid sequence or “genetic code” of the defective gene to restore the correct functional version. Thus, this replacement therapy could eliminate the hereditary risk associated with the defective BRCA genes and prevent the prophylactic removal of organs.
Another gene implicated in cancer is not a mutated gene; rather it’s an over-expressed gene, known as HER-2. This gene stimulates cell proliferation and, when over-expressed, increases the risk of developing breast cancer. Much research has focused on targeting and silencing this gene, as it has been found that the level of HER-2 gene is over-expressed in 15-20% of patients with breast cancer (Breast Cancer). Researchers are looking for ways to synthesize drugs that target and silence these genes and prevent them from over-expressing before the disease develops. Such research is already underway, as an antibody called “herceptin” has been synthesized to target and silence the over-produced protein made from HER-2 (Privalsky).
Gene silencing, another exciting approach to prevent mastectomies and lumpectomies, is being developed at Harvard University. This research involves injections of RNA interference particles (RNAi) into the breasts of mice to turn off the “HoxA1” gene, which has been labeled as an oncogenic gene (Ferber). Their results so far have shown that as few as 25% of the mice injected with the RNAi develop cancer, as opposed to 100% of the control mice, all of which developed breast cancer (Ferber). This procedure is still far from human trials, and further funding is needed, but it shows promise.
In the words of Don Ingber, M.D., Ph.D, of the Wyss Institute of Biologically Inspired Engineering at Harvard, “The idea would be start giving it early on and sustain treatment throughout life to prevent cancer development or progression” (quoted in Ferber). The availability of effective sustained treatments would give men and especially women a peaceful state of mind, especially if they have an increased hereditary risk of developing the disease.
Such new, exciting treatments could prevent the need for surgical, prophylactic removal of organs and could minimize “chemoprevention.” Some doctors recommend chemoprevention to prevent breast cancer, especially for women with an increased hereditary risk. Chemoprevention is the administration of vitamins, Tamoxifen, aspirin, or other substances to reduce the risk of developing the disease (chemoprevention). Many of these drugs have chronic side effects. Tamoxifen, for example, blocks estrogen receptors, thus reducing the activity of estrogen (“the bone protecting hormone”). As a result, many women on Tamoxifen have a low bone density and must take calcium supplements to relieve their symptoms of osteoporosis.
Breast cancer and cancer research in general is on the verge of making a quantum leap forward, as researchers are looking for ways to alter the defective gene prior to it waking up from its slumber, or by developing a medication that will target the diseased cell’s distinctive amino acid sequence, thereby eliminating only the diseased cells.
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Privalsky, Martin. “Cancer.” Cell Biology. UC Davis. Haring Hall, Davis. 5 May 2014. BIOLSCI 104 Class lecture.
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