Science reached a historic milestone in 2003, after decades of careful study and discoveries about DNA — the hereditary material housed in the nucleus of virtually every cell in the human body — with publication of the Human Genome Project. Since that basic encyclopedia of what makes us human was compiled, scientists have set about finding ways to tinker with the genetic code in hopes of finding cures for diseases like breast cancer. That’s led to the development of technologies that one day may allow doctors to stop cancers before they even begin — by editing DNA in people who carry certain mutations that predispose them to cancer — or by treating cancer after it’s begun by harnessing the power of the body’s immune system to fight cancer cells through gene editing.
One such technology, which entered the sphere of public awareness in 2013, is CRISPR. The Harvard University ” Science in the News” blog describes CRISPR as a technology “that facilitates making specific changes in the DNA of humans, other animals and plants.” CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeat, which “refers to the unique organization of short, partially palindromic repeated DNA sequences found in the genomes of bacteria and other microorganisms.” In other words, the building block molecules that line up in specific orders to create genetic code.
[See: 16 Health Screenings All Women Need.]
So how can this technology aid in the treatment of complex disease with a genetic component? As The Canadian Cancer Society explains, “scientists can now permanently modify genes in living cells and hopefully in the future correct mutations — like fixing typos — in the human genome to treat the genetic causes of disease. Although researchers have used other gene editing techniques in the past to modify cells, CRISPR is simpler and more efficient, which promises to speed up the process of using gene-edited cells in the clinic.”
The use of a system called CRISPR-Cas9 could hold implications for the treatment of a range of diseases that contain a genetic component to them, including breast cancer. All cancers begin with a cell gone haywire when replicating itself, and those mistakes happen in the genes. It’s still very early in development, but not too soon to imagine that sometime in the future, carriers of mutations on the BRCA1 and BRCA2 gene may be offered prophylactic gene editing rather than prophylactic bilateral mastectomies to reduce their risk of developing breast and ovarian cancer. The Centers for Disease Control and Prevention reports that 50 percent of women with a BRCA1 or BRCA2 gene mutation will develop breast cancer by age 70. That’s compared to about 7 percent of women in the general population.
And other patients with breast cancer may be offered gene editing as part of a complex immunotherapy approach to treating cancer that is not related to a BRAC1 or BRCA2 gene mutation. By removing cells from the body, editing them in the lab, and reinserting them into the body, they can then go on attack against cancer cells. Theoretically, this approach could have fewer side effects, because the patient’s own cells are being used to lead the charge, but these sorts of treatments are still a very long way off.
[See: 7 Innovations in Cancer Therapy.]
The first clinical trial of this application of CRISPR-Cas9 technology in humans (with lung cancer) is underway in China, and a U.S. trial in cancer patients is slated to begin in patients 2018. A 2016 Nature article describes how the U.S. trial, which is intended to primarily ascertain the safety of the approach rather than its effectiveness, should work: “The researchers will remove T cells from 18 patients with several types of cancers and perform three CRISPR edits on them.” T cells are produced in the thalamus gland, hence the name T cell, and they’re integral to the immune system’s response to infection. “One edit will insert a gene for a protein engineered to detect cancer cells and instruct the T cells to target them, and a second edit removes a natural T-cell protein that could interfere with this process. The third is defensive: it will remove the gene for a protein that identifies the T cells as immune cells and prevent the cancer cells from disabling them. The researchers will then infuse the edited cells back into the patient.” Those cells will then, theoretically, go on to do battle against cancer in the body. It’s a clever way of using the body’s natural defense mechanisms to beat cancer.
These trials are important, because so far, the technology has worked well using cell specimens in the lab, but transitioning into a whole organism is a much different scenario. A study published in the journal Nature Methods in May 2017 found that unintended mutations can slip into the mix when gene editing is being deployed. According to a press release issued by Columbia University Medical Center, where the study was conducted, “even though CRISPR can precisely target specific stretches of DNA, it sometimes hits other parts of the genome. Most studies that search for these off-target mutations use computer algorithms to identify areas most likely to be affected and then examine those areas for deletions and insertions.”
The CUMC press release indicates that the technique had successfully corrected the gene that researchers were trying to edit — one that causes blindness — but by sequencing the whole genome afterwards, the research team also observed mutations they didn’t expect to find, and ones the computer algorithm hadn’t predicted.
Although these changes didn’t result in any obvious short-term problems for the mice that had received the gene editing, it’s clear that further testing is needed before these technologies will be deployed as a regular approach to treating any human disease.
[See: What Not to Say to a Breast Cancer Patient.]
In addition to concerns about unintended side effects or genetic alterations that could cause unexpected problems, there are also many bioethical questions being raised about the use of gene editing technology, particularly when it comes to editing genes in an embryo before implantation. Some researchers say that just because we can alter the genetic code doesn’t mean we should. According to a report from the Bioethics Observatory at the Institute of Life Sciences, a program of the Catholic University of Valencia in Spain, some researchers are concerned that in the effort to combat cancer, mistakes made during the gene editing process could actually accelerate the development of other cancers.
Nevertheless, there’s still plenty of reason to be optimistic about the potential that gene editing holds for the future of medicine and the treatment of breast cancer. Although CRISPR is not likely to be a therapeutic approach you’ll be offered anytime soon, many scientists and doctors believe this revolutionary technology could signal the next frontier in personalized medicine.
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What Might CRISPR and Gene Editing Mean for Breast Cancer? originally appeared on usnews.com
