Code to Cure

Cancer

What exactly is cancer? Cancer disease is the result of cells growing uncontrollably and spreading to the other parts of the human body. Cancer can start almost anywhere in the human body, which is made up of trillions of cells. Normally, human cells grow and multiply through a process called cell division, to form new cells as the body needs them. When cells grow old or become damaged, they die, and new cells take their place. Sometimes this orderly process breaks down, and abnormal or damaged cells grow and multiply when they shouldn’t. These cells may form tumors, which are lumps of tissue. Tumors can be cancerous or not cancerous (benign). Cancerous tumors spread into, or invade tissues and continue to form new tumors around the body. Benign tumors do not travel around the body or invade tissues and when removed they don’t usually grow back unlike cancerous (malignant) tumors. Though benign tumors may be dangerous if they are present in vital organs such as the brain. 

There are more than 200 types of cancers that can be found in the body. With the most crucial ones to our lives being esophageal, liver, lung, acute myeloid leukemia, brain, nervous system, stomach, ovarian and pancreatic cancers. Gene therapy, which is still in development, is said to be the cure for lung and pancreatic cancer.

Genetic Engineering

To fully understand the potential of genetic engineering in cancer treatment, it is important to first explore the concept of genetic engineering itself. Genetic engineering, also known as genetic modification, manipulation and recombination is a process that uses laboratory-based technologies to alter the DNA makeup of an organism. This may involve changing a single base pair (A-T or C-G), deleting a region of DNA or adding a new segment of DNA. For example, genetic engineering may involve adding a gene from one species to an organism from a different species to produce a desired trait. Used in research and industry, genetic engineering has been applied to the production of cancer therapies, brewing yeasts, genetically modified plants and livestock, and more. In 1973, biochemists Herbert Boyer and Stanley Cohen used genetic modification by inserting DNA from one bacteria into another. Though the concept of genetic engineering was first proposed by Nikolay Timofeev-Ressovsky in 1934. In the first few years of the existence of such technology, genetic engineering has been used in editing plant genes to make them stronger and resistant to pests and herbicides. 

In the early 1990s, scientists started to test gene editing on humans to treat genetic diseases like cancer.

Now, according to the National Institutes of Health, with the current round of ongoing clinical trials, the potential of gene therapy cancer vaccines is close to being fulfilled. The current techniques that are being used or in development are known as CRISPR-Cas9, CAR-T cell therapy, Oncolytic viruses and gene silencing. Delving into these innovative treatments, CRISPR-Cas9 might be the most mesmerizing one of them all. With the CRISPR tool, it will be possible to edit genes by precisely cutting DNA and then harnessing natural DNA repair processes to modify the gene in the desired manner. The system has two components: the Cas9 enzyme and a guide RNA. After this technology is fully developed in lab trials, CRISPR is guessed to be the cheapest genetic engineering treatment of them all that would be more accessible to cancer patients around the globe. CAR-T cell therapy involves genetically engineering a patient's own T cells to attack cancer cells. In biology chimeric antigen receptors (CARs), also known as chimeric immunoreceptors, chimeric T cell receptors or artificial T cell receptors are receptor proteins that have been engineered to give T cells the new ability to target a specific antigen. The receptors are chimeric in that they combine both antigen-binding and T cell activating functions into a single receptor. The process of CAR-T cell therapy goes on like; collecting your T-cells, converting your T-cells into CAR T-cells at a special laboratory, growing your CAR-T cells in the laboratory, preparing your body for the CAR-T cells, infusing the CAR-T cells into your body, and lastly monitoring you for potential complications after treatment. In a basic matter, Doctors take a patient's own immune cells (T cells), genetically modify them in the lab to better recognize and attack cancer cells, and then put them back into the body. CAR-T cell therapy is already in use for blood cancers like leukemia and lymphoma. Another technology that is in use is oncolytic viruses. An oncolytic virus is a virus that preferentially infects and kills cancer cells. Scientists engineer these viruses to specifically infect and kill cancer cells, leaving normal cells alone. For instance, The FDA-approved T-VEC, a modified herpes virus, is used for treating melanoma (a type of skin cancer). In theory, there is a technology that allows scientists to basically mute the cancer genes called oncogenes. Gene silencing, inhibits the expression of specific genes, preventing them from producing corresponding proteins. In cancer treatments, this approach is used to suppress genes that drive tumor growth, survival, or metastasis, particularly oncogenes. Some gene-silencing drugs are in clinical trials. A few, like Patisiran (for another disease), are already approved, and now researchers are adapting the tech for cancer. 

Once the scientific basis of genetic engineering is understood, it is important to examine how these technologies are applied to cancer treatment. In recent years, advances in gene editing and cell-based therapies have allowed the development of groundbreaking methods that are already being used in clinical settings. These treatments aim not only to eliminate cancer more effectively, but also to provide personalized treatment specific to each patient's genetic makeup. In this section, current applications such as CAR-T cell therapy and CRISPR-based methods will be discussed and the effectiveness, advantages, and limitations of these approaches will be evaluated.

Genetic engineering-based cancer treatments have achieved significant success, especially in blood cancers such as leukemia and lymphoma. However, today, scientists are investigating whether these innovative methods can be applied to other types of cancers that are not limited to blood cancers but also to solid tumors. In this context, cell therapies, oncolytic viruses and the developing CRISPR technology have promising potential in common and difficult-to-treat cancer types such as lung, pancreatic, brain and breast cancer.

Although CAR-T cell therapy is quite effective in blood cancers, the same success has not yet been achieved due to the difficulties encountered in solid tumors. Solid tumors have a protective microenvironment around them that blocks immune cells. This makes it difficult for genetically programmed T cells to reach the tumor and attack it effectively. However, next-generation research is working on genetic modifications that will allow T cells to overcome this microenvironment. For example, in a clinical trial conducted in 2022, patients with advanced pancreatic cancer were given modified CAR-T cells and tumor shrinkage was observed in some patients. This is important in terms of showing the potential of the method.

As mentioned before, oncolytic viruses are genetically modified viruses that only infect and destroy cancer cells and also activate the immune system. These viruses help the immune system fight the tumor more effectively. The oncolytic virus called Talimogene laherparepvec (T-VEC), which is currently used in some types of cancer such as melanoma (skin cancer), has shown clinical success. It is now being investigated whether similar viruses will be effective in other types of cancer such as brain tumors, breast cancer and lung cancer. Oncolytic viruses can also be used in combination with other treatments (chemotherapy, immunotherapies) to increase the effectiveness of the treatment.

CRISPR-Cas9 is a highly sensitive gene editing technology that allows cancer to be targeted at the genetic level. Although the first studies were generally conducted on blood cells, it is now thought that this technology can also be used against solid tumors. In particular, genetically editing immune cells with CRISPR can make them more resistant and effective. In addition, strategies such as directly changing the genetic structure of tumor cells, stopping cells from dividing or making the tumor more visible are being studied.

In a study conducted in China in 2020, CRISPR-edited T cells were applied to patients with lung cancer and the patients responded positively to the treatment. This is an important first step in the use of CRISPR in solid tumors. However, there are still many dimensions that need to be investigated in terms of safety, ethics and long-term effects. 

Although genetic engineering offers great promise in cancer treatment, many ethical, scientific and technical issues related to the use of these technologies remain unresolved. Cell therapies, oncolytic viruses and methods such as CRISPR are powerful technologies that can transform human life. However, the responsibility that comes with this power necessitates careful evaluation.

One of the most debated issues in genetic engineering is the limits of genetic editing. Although genetic interventions used in cancer treatment are mostly limited to somatic cells, there is a risk that these technologies will shift to controversial areas such as genetic selection, creating genetic advantage or changing human characteristics in the future. The use of powerful tools such as CRISPR in human embryos is considered unethical and legally prohibited in many countries.

In addition, issues such as the environmental effects of oncolytic viruses, the risk of side effects, the transparency of clinical tests and the equal accessibility of treatments should also be carefully considered from an ethical perspective. The availability of such advanced treatments only in certain countries or in individuals with high socioeconomic status may increase global health inequalities.

Genetic engineering-based treatments are still experimental and contain many unknowns. The complex structure of solid tumors makes it difficult for the immune system to access these tumors, which limits the effectiveness of CAR-T cells. Another scientific problem is the risk that oncolytic viruses can harm healthy cells outside the tumor. In addition, situations such as the CRISPR system intervening in the wrong regions ("off-target effects") can create potential side effects.

These challenges necessitate further research, development, and clinical trials. In addition, these technologies need to proceed with ethically approved and transparent processes in order to monitor their long-term effects.

Despite all these challenges, genetic engineering has a high potential to revolutionize cancer treatment. Scientists aim to develop customized treatment protocols by customizing the genetic code of cells. This supports the vision of a healthcare system in the future where the most appropriate and effective treatment can be applied to each patient.

The combination of artificial intelligence and genetic engineering can enable faster identification of cancer cells and more sensitive responses to treatment. In this way, cancer can become a disease that can not only be treated but also prevented in the early stages more efficiently.