According to the National Cancer Institute, in 2019 alone, 1.8 million people would be diagnosed with cancer, and that’s just in the United States. Of these 1.8 million people, 606,880 won’t make it to see themselves win the battle. Of these 1.8 million people, the majority would have to endure some combination of treatment to combat such a disease whether it’s surgery, chemotherapy, or radiation. The majority of these 1.8 million people would have to experience both mental and physical fatigue, weight loss, hair loss, nausea, vomiting, memory and concentration loss, and so much more. For decades, researchers have been looking for a solution that minimizes both effects and incidences, and they might have found just the trick in the form of gene therapy.

Now let’s get familiar with the common forms of cancer treatments.

Surgery removes the cancer and associated tumors and does this by either cutting through skin, muscle, or bone, using cold liquid nitrogen to freeze off abnormal tissue, applying laser beams to tissues or masses to shrink and remove them, or exposing the cells and tissues to extreme heat to kill or weaken what’s present. As for the aftermath of the procedure, along with varying recovery time and surgeon visits, the patient might experience pain, infection, damage to nearby healthy tissues, and bleeding. However, doctors tend to turn to this tactic first in order to have the chance to remove the entire tumor, debulk it, or ease symptoms.

Chemotherapy is typically administered intravenously and treats the cancer by targeting rapidly dividing cells. With such a method, a patient is often confined to a hospital chair anywhere from half an hour to four hours, then left to suffer the hair loss, appetite loss, nausea, diarrhea, and anemia at home for days to weeks at a time before the next round. The ultimate goal of chemotherapy is to get rid of all the cancer cells, eradicating the cancer completely, but others include getting rid of potential cancer cells that might remain after surgery, shrinking the tumor before surgery, and relieving the symptoms and slowing down the growth for those whose development has gone too far.

Radiation therapy involves the use of high doses of radiation in order to damage the DNA of the cancer cells significantly enough to cause them to stop replicating. There are two kinds of radiation therapy: external beam and internal radiation. With an external beam, the patient is to lay down on a table and a machine will move around them to release radiation at certain parts of the body. With internal radiation, the patient is to swallow or be injected with a source of radiation near the tumor site and that radiation will damage the cancer cells from the inside. Each radiation therapy session lasts between 10 to 30 minutes, with several weeks in between sessions, and the patient is left with various types of side effects depending on the location of the tumor; however, some include fatigue, hair loss, skin discoloration, swelling, shortness of breath, diarrhea, and blurry vision. The goal of radiation is the ease the symptoms of the patient, prevent a cancer from returning, and killing/slowing the cancer that is present.

What makes gene therapy so special compared to the current treatments is its mode of attack. Unlike, surgery, chemotherapy, and radiation, gene therapy attacks cancer cells by implanting itself in the core, the genes in the DNA, and altering its expression. In order to do so, scientists employ viral particles or adenoviruses, such as herpes, that are genetically modified to contain a certain genetic expression, so, when injected, the particle is able to go into the cancer cell’s DNA and turn on or off the genetic sequence that is causing it to replicate or form defective proteins, or is able to go into a healthy cell to boost its fighting strength.

Currently, there are three versions of gene therapy: gene transfer, immunotherapy, and oncolytic viral therapy.

Gene transfer consists of the introduction of new genes within the surrounding tissue or cancer cell, typically through intravenous injection. The purpose of gene transfer is to program these viral particles to limit cell growth or just all together cause cell death.

Immunotherapy manipulates a patient’s immune system by stimulating it to aid in fighting and destroying cancer cells. This method is able to perform such tasks by adding the specific genes to the patient’s own blood or bone marrow cells, a viral particle, or a vaccine with manipulated cells. The purpose of immunotherapy is to use the patient’s own immune system to combat the disease rather than using foreign chemicals or rays that can suppress it further.

Oncolytic viral therapy is best suited for the more metastatic cancers because of the replicated nature of both the cells and viral particles. When the viral particles get placed into the body, they invade the rapidly dividing cells, so the viral particles replicate fast within them as well, causing cell destruction.

However, like other treatments, limitations exist, more so with immunotherapy and oncolytic therapy, but there are not as many present in gene therapy like there are in others.

As described by Dr. Deanna Cross and James K Burmester in “Gene Therapy for Cancer Treatment: Past, Present, and Future,” the concern with immunotherapy comes from the vaccination aspect. Since the engineered cells used for the vaccines originate from the individual, it costs a lot of money and takes a substantial amount of time to create and uphold, and very few facilities possess such tools to manufacture the product, thus availability is limited and production might not be able to catch up with the rate of disease.

Moreover, in order for oncolytic therapy to be effective, the viral particles have to be able to out-grow the cancer growth, which is harder for more set masses, therefore, this treatment might have to be paired alongside another. In addition, this method is still relatively new so some key factors, such as the most effective virus to deliver the new genetic message, is still unknown.

Comparatively, gene therapy is associated with fewer side effects since it is more direct at targeting certain cells, maintaining the health of the unaffected, however, that doesn’t eliminate the notion that there aren’t any.

The main side effect that is of concern is toxicity, more specifically, severe adverse effects. There have been cases where after the injection, there has been an increase in certain protein levels, in turn, causing other conditions such as disseminated intravascular coagulation (small clots in the bloodstream) or leukemia. However, it is still unclear on whether it is the gene therapy treatment that is causing these severe adverse effects, or the environment and other genes that the patient may possess. On top of that, it’s hard to predict the severity of the toxicity because the animals used for testing, athymic or SCID mice, lack an immune system which would show the severity effects.

The other main side effect of concern is the replication of the recombinated viruses, a virus with recombined pieces of DNA, used for treatment. If the viruses used to impose treatment were to recombinant and then replicate, then the antibiotics necessary to regulate the problem wouldn’t be available since they do not exist yet, leading to further illness.

Rest assure that such cases have other confounding variables attached to it, so though it happened to a genetic therapy patient, it does not conclude that those effects are a direct result from the treatment itself. As often reiterated and heavily emphasized in science, correlation does not equal causation.

 

Overall, gene therapy is still a relatively new topic, undergoing clinical research trials as we speak, and yet, Dr. Amer showed that it has already been linked to success in chronic lymphocytic leukemia, acute lymphocytic leukemia, and brains tumors.

Once enough research is done to improve on the three types already present, as well as the development of other types, it can be used alongside other treatments or by itself to manage cancers.

Gene therapy possesses the ability to treat a disease like cancer at its base and tailored to the individual, in turn allowing for a more effective and definite fix by stopping the growth and expressing the proper protein to restore normal function. With such qualities, it has the potential to eradicate and prevent the hereditary nature of cancer and be an overall cure to cancer.

Gene therapy will win the battle against cancer for those who couldn’t and protect those from ever having to fight that battle again.

 

 

 

 

 

 

 

 

References

“Acute Lymphocytic Leukemia.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 10 Aug. 2018, https://www.mayoclinic.org/diseases-conditions/acute-lymphocytic-leukemia/symptoms-causes/syc-20369077

“Chronic Lymphocytic Leukemia.” Mayo Clinic, Mayo Foundation for Medical Education and Research, 3 Apr.2019, https://www.mayoclinic.org/diseases-conditions/chronic-lymphocytic-leukemia/symptoms-causes/syc-20352428

“Common Cancer Sites – Cancer Stat Facts.” SEER, seer.cancer.gov/statfacts/html/common.html.

“Gene Expression.” Genome.gov, www.genome.gov/genetics-glossary/Gene-Expression.

“How Does Chemotherapy Work?” InformedHealth.org [Internet]., U.S. National Library of Medicine, 15 Aug. 2019, www.ncbi.nlm.nih.gov/books/NBK279427/.

“Information for Health Care Providers.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 7 Nov. 2019, www.cdc.gov/cancer/preventinfections/providers.htm.

“Radiation Therapy for Cancer.” National Cancer Institute, www.cancer.gov/about-cancer/treatment/types/radiation-therapy#RTCCSE.

“Side Effects of Cancer Treatment.” National Cancer Institute, www.cancer.gov/about-cancer/treatment/side-effects.

“Surgery for Cancer.” National Cancer Institute, www.cancer.gov/about-cancer/treatment/types/surgery#WEBDAS.

Amer, Magid H. “Gene therapy for cancer: present status and future perspective.” Molecular and cellular therapies vol. 2 27. 10 Sep. 2014, doi:10.1186/2052-8426-2-27

Chulpanova, Daria S, et al. “Recombinant Viruses for Cancer Therapy.” Biomedicines, MDPI, 25 Sept, 2018, www.ncbi.nlm.nih.gov/pubmed/30257488

Cross, Deanna, and James K Burmester. “Gene therapy for cancer treatment: past, present and future.” Clinical Medicine & Research vol. 4 iss.3 (2006): 218-27. doi:10.3121/cmr.4.3.218

Hunt, Kelly K., et al. Gene Therapy for Cancer. Humana Press, 2007. IBSN: 978-1-58829-472-2

Wold, William S M, and Karoly Toth. “Adenovirus vectors for gene therapy, vaccination and cancer gene therapy.” Current gene therapy vol. 13,6 (2013): 421-33. doi:10.2174/1566523213666131125095046

By: E. Melbouci

Image Credits

Stepanenko Oksana, Gene therapy DNA 3D chemical molecule structure low poly. Polygonal triangle point line healthy cell part. Innovation., Dreamstime, https://www.dreamstime.com/gene-therapy-dna-d-chemical-molecule-structure-low-poly-polygonal-triangle-point-line-healthy-cell-innovation-blue-medicine-genome-image115746910