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The Fight Against Cancer: Gene Therapy
- Project Medify
- Sep 2, 2020
- 6 min read
By Arush Mishra
Abstract
Humankind has faced several hardships throughout its existence. Whether these dilemmas be terror, famine, or even war, humans have found a solution to every problem that has come their way. However, our most profound enemy resides within our own bodies. Cancer, an illness caused by rapid uncontrollable cell division, is an age-old predicament that scientists still have not fully found an answer to. Over the centuries, particularly in the past few decades, experts have found ways to slow down the progression of this disease, and yet according to the American Cancer Society, “...there will be an estimated 1.8 million new cancer cases diagnosed and 606,520 cancer deaths in the United States,” in the year 2020 alone. To put these statistics into perspective, cancer is predicted to take 1662 human lives every day. Although with new treatments and discoveries this number is destined to decrease in the future, mankind will not truly have won this war without finding a cure. Even though this cure may be far off, doctors and scientists have made a breakthrough in gene therapy that could very well turn the tide in humans’ favor in the fight against cancer.
How does Gene Therapy Work? As previously mentioned, cancer proliferates by eliciting cells to enter a state of rapid cell division. This occurs due to a mutation in a cell’s DNA. While normal cells have a lifespan after which they enter lysis (cell death), cancer cells do not. This means that through accelerated mitosis, they can form clumps called tumors. Tumors inhibit specific organ functions, and, if left untreated, eventually result in death. One of the most common treatment options is chemotherapy. Chemotherapy (or “Chemo”) involves the intravenous (IV) infusion of harsh chemicals to destroy cancer cells, effectively shrinking tumors. However, it often has grueling side effects which include:
Fatigue
Hair loss
Easy bruising and bleeding
Infection
Anemia (low red blood cell counts)
Nausea and vomiting
Appetite changes
Constipation
Diarrhea
Gene therapy utilizes a patient’s body in a safer manner. Rather than destroying the cancer cells using harsh drugs and chemicals, gene therapy involves altering specific DNA sequences in the cells of affected patients. Since this method is a lot more focused, it has little to no effect on the body over the course of the treatment. In addition, there is a variety of gene therapy that can boost the immune system, make cancer cells more susceptible to other treatments, and prevent replication by invoking lysis.
Gene Therapy: Boosting the Immune System
Immunotherapy, gene therapy to boost the immune system, helps the body’s own immune system combat cancerous cells. In an untreated form of cancer, cancer cells are able to change the membrane proteins located on their surface in order to “hide” from the immune system. By using a version of immunotherapy known as CAR T cell therapy, leukocytes (white blood cells) known as T cells are modified to better fight against the metastasizing cancer. According to WebMD.com, “First, a machine filters T cells out of your blood, then it puts the blood back into your body. (This process is called apheresis.) The T cells are sent to a lab, where the genes inside them are changed: They’re told to make proteins called CARs…” CARs are special membrane proteins that are able to attach to cancerous cells, allowing leukocytes to more effectively eliminate the cancer. Since doctors are given the ability to directly modify the patient’s blood cells, there are much fewer side effects than there are with chemo or hormonal therapy.
Another option to help the immune system resides within the field of epigenetics. Epigenetics basically deals with a cell’s ability to silence or deactivate certain genetic codes. In a process known as DNA methylation, a cell can “turn off” the promoting regions of certain genes, therefore preventing said genes from being expressed. According to ncbi.nlm.nih.gov, “[DNA Methylation] provides a stable gene silencing mechanism that plays an important role in regulating gene expression and chromatin...”In cancer cells, this process is altered such that the genes responsible for creating the appropriate CAR proteins are silenced, effectively hiding the cancer from a patient’s immune system. This presents a major problem, as once again it inhibits the body’s ability to properly combat a tumor. Nonetheless, doctors and scientists have made a breakthrough. By developing certain “epigenetic drugs”, doctors are able to properly restore DNA methylation to its normal function. In this way, cancer cells will become visible to a patient’s leukocytes, whereas healthy cells will resume normal function.
Gene Therapy: Weakening Cancer Resistance
Another method used by doctors involves altering the genetic code of the cancer cell itself. Cancer cells -like normal cells- can develop a resistance to a particular drug. This can make it even harder to treat cancer. However, by altering the genetic code of a group of cancer cells, the tumor can become less immune to some drugs. According to cell.com, “[The process] involves the insertion of a gene encoding a drug-metabolizing enzyme into cells and the systemic administration of a prodrug. The prodrug is converted to a cytotoxic agent by the action of the expressed enzyme.” In other words, by inserting a gene that produces a “drug-helping” enzyme, anti-cancer drugs will act faster and have a greater efficacy than against a standard cancer cell. Once again, side effects are minimal since the gene is inserted into a handful of cells at a time, and each gene is unique to each cluster of cells. This means other cells will not be affected by said gene.
Gene Therapy: Inducing Lysis
Perhaps the most direct way of dealing with cancer via gene therapy is to cause the cancer cells to kill themselves. This is done by inducing lysis, or cell death, in cancer cells. Keep in mind that cancer cells have a mutated form of the gene that controls lifespan. In theory, by injecting this gene back into the cancer cells, they will kill themselves in a process known as apoptosis, as they have already exceeded their lifespan.. In this way, healthy cells are left alone, whereas cancer cells are eliminated. The gene is injected into the cell by means of oncolytic viruses. These viruses are specifically engineered to deliver the normal gene into cancer cells without infecting healthy cells. According to the Dana-Farber Cancer Institute Blog, “In animal studies, such viruses have achieved promising results in a variety of cancers, including colon, bladder, and osteosarcoma (a form of bone cancer)...” Although this mode of gene therapy is very promising, there is a catch. The main problem is that the viruses used to infect cancer cells are often recognized by the immune system as a threat, and as such are often destroyed. In order to properly use this type of gene therapy, it is crucial that scientists discover how to administer the virus in a form that will either bypass or trick the immune system. For example, doctors may choose to administer this treatment in a way that will only target one specific type of cell. A typical target would be a type of cell more prone to mutations, such as a stem cell. According to harvard.edu, “Stem cells survive much longer than ordinary cells, increasing the chance that they might accumulate genetic mutations. It might take only a few mutations for one cell to lose control over its self-renewal and growth and become the source of cancer." Since the treatment would hypothetically be introduced in small, targeted amounts, the immune system would have a harder time detecting the oncolytic virus, making this treatment all the more effective.
Discussion
Cancer is a deeply rooted problem. Small changes in one’s molecular DNA can yield devastating consequences, and there is no way of stopping it. Patient cases and deaths are constantly rising in number, and this may seem like a reason to give up. Nevertheless, humanity perseveres. Through tireless efforts and unbending dedication, doctors and scientists are discovering new and innovative ways to combat cancer. Although there is still much to learn, one thing is for certain. With new advancements in medicine such as gene therapy, people are prepared now more than ever to win the fight against cancer.
Sources
“Cancer Statistics.” National Cancer Institute, www.cancer.gov/about-
“Chemotherapy Side Effects.” American Cancer Society, www.cancer.org/treatment/treatments-
“General Cancer Information.” Gene Therapy | Cancer in General | Cancer Research UK, 14 Nov.
“How Is Gene Therapy Being Used to Treat Cancer?: Dana-Farber Cancer Institute.” Dana, 12 \
Rigg, Anne. “Genetic Prodrug Activation Therapy.” Trends in Molecular Medicine, 1997,
“Stem Cells and Cancer.” Harvard Stem Cell Institute (HSCI), hsci.harvard.edu/stem-cells-and-
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