BRONZE

Genetic switches as a cancer treatment

I am researching genetic switches; how they work and how genetic switches can be applied in cancer treatment.
Zaria Huq
Grade 8

Problem

In Canada, one in two people is expected to develop cancer at some point in their life. There are many cancer treatments, but many of these treatments are very invasive and have dangerous and long lasting side effects. Scientists are studying new ways to treat cancer. In this research project, I am studying one of these ways: How genetic switches could be used in cancer treatment.

Method

Research Methods

  • I will be studying and researching genetic switches and their application in the real world using google, academic archives and reputable websites and magazines.
  • At first I started using google scholar, but the search returned was very high-detail, advanced articles, so I made the choice to use a regular google search, and have more understandable results.
    • I used the search term “cancer treatment with genetic switches”
      • I went through the first 2 pages of the search results finding relevant articles from reputable sites.
      • From my search I found many media reports, and most of them had a study attached. I used the studies attached to gain a deeper understanding of the information I found in the media report.
      • Each of these links are persented in my citations section in proper reference format

Media report

Research paper

https://www.medicalnewstoday.com/articles/321646

https://pubs.acs.org/doi/10.1021/acssynbio.7b00455 

https://www.caltech.edu/about/news/taking-closer-look-genetic-switches-cancer-72197 

https://authors.library.caltech.edu/77629/ 

https://www.nature.com/articles/s42003-020-0971-8 

https://www.nature.com/articles/s42003-020-0971-8 

https://www.dana-farber.org/newsroom/news-releases/2021/scientists-create-on-off-switches-to-control-car-t-cell-activity/ 

https://www.dana-farber.org/newsroom/news-releases/2021/scientists-create-on-off-switches-to-control-car-t-cell-activity/ 

https://labblog.uofmhealth.org/lab-report/turning-on-off-switch-cancer-cells 

https://labblog.uofmhealth.org/lab-report/turning-on-off-switch-cancer-cells 

https://med.stanford.edu/news/all-news/2018/10/study-identifies-link-between-dna-protein-binding-cancer-onset.html 

https://med.stanford.edu/news/all-news/2018/10/study-identifies-link-between-dna-protein-binding-cancer-onset.html 

 

 

 

Research

Currently, the most common cancer treatments are surgery, chemothereapy, radiation therapy, and stem cell transplants. Surgery is quite risky, and requires often extensive recovery time. Chemotherapy attacks all cells that rapidly reproduce, which is why hair cells, skin cells, and immune system cells are targerted as well as the cancer cells. Radition therapy is also very risky, as the healthy tissues around the tumor can be easily damaged by the radation.

A new idea for cancer treatment that is being explored by scientists is to use genetic switches to stop or turn off the switch that causes healthy cells to multiply rapidly and become cancerous tumors. The idea is that cancer switch treatment would be less invasive than chemotherapy, as it would only target the cells that were causing the cancer, not any and all cells that rapidly multiply, like skin cells, hair cells, and immune system cells (e.g. white blood cells). 

Genetic switches are part of gene regulation process, which is very complex. Here is a simplifed explaination of the process of gene regulation.

When the DNA is read by a RNA polymerase, generally the final product is a strand of mRNA that is broken up and read by more RNA polymerase to create an enzyme that will determine a feature of an organism. In the DNA there is a promoter, where the RNA polymerase attaches. There is also a operator or an on off switch. Sometimes, a repressor will bind to the operator, turning the switch off. In turning the switch off, the RNA polymerase is not able to move past the operator, not able to read the DNA and consequently, not able to produce the enzyme that strand of DNA was coded for. This repressor is made regularly, but usually is in a inactive state. If tryptophan (an enzyme) binds to the inactive repressor, the shape changes shape to bind to the promoter.  To take the repressor off of the operator, an allolactose (another enzyme) will attach to the repressor and deactivate it. This allows the RNA polymerase to continue reading the DNA. So, if we find the mutation in the DNA that is creating the cell multpication, and we turn off the switch (fix the mutation) we will be able to stop the cells from replicating so rapidly they become tumors. 

There are a few new ideas for the use of genetic switches as a treatment for cancer.

( https://www.caltech.edu/about/news/taking-closer-look-genetic-switches-cancer-72197  )

At CALTECH University, scientists are studying how to mutate genes in a lab, the idea is that in time, they could introduce  rthe mutated part of a cell's gene into patients with leukemia to cure their leukemia. Leukemia is a type of cancer where there is an abundance of blood cells. In the leukemia specified in the article, acute myeloid leukemia, there is a large amount of blood stem cells. Before the blood cells become specific red or white blood cells, the stem cells are immortal, meaning they don't die off. A protein called DPF2 is the on/off switch for the production of blood stem cells. If the switch is on, the production of blood stem cells does not turn off, which creates an overflow of blood stem cells. When there is an overflow of blood stem cells, the many stem cells stop oxygen from reaching red blood cells. The overflow of cells can also create tumors if they congregate. The CALTAF scientists mutated a DPF2 protein, which was able to turn off stem cell production. Scientises are not sure if this mutated DPF2 protein will turn the stem cell production switch off in cancer patients, but that is the hope.

(https://www.webmd.com/diet/foods-high-in-tryptophan#1 )

Another application of genetic switches in cancer treatment is tryptophan specific repressors. These will turn off a different kind of genetic swtch, one that has tryptophan specific repressors. Like in the above example, if a cell with a mutation is multiplyed, each cell it multiplys into will have the same mutation resulting in quick spreading cell replication and eventually cancer. Cancer switch treatment would target the trypophan repressor, turn it off, and stop the cell from multiplying.

Interestingly, tryptophan is an amino acid that is created in the body. It is obtained with a specific diet, including milk, which has 732 milligrams of Tryptophan per quart. Other foods with tryptophan include tuna, chicken, and turkey. A diet with specific foods such as these could potentially prevent cancer, by activating the repressor and turning off the swith. Imagine, food as a cure for some kinds of cancer! 

 

Data

I am not providing data as this is a research project where no data was collected.

Conclusion

As genetic switches are a new area of science, I believe that they will end up being a very valuable addition to cancer treatments. My hope is that they will be a safe, effective, non-invasive solution for patients with cancer. Given that most scientists are conducting bench researching right now, I can assume that it will be around 5-10 years until a solid, effective treatment will emerge from cancer switch research. If I was going to start to make a cancer treatment, I would start by writing a study with a lab report included, then I would choose which type of repressor I would use to switch off the DNA. Possibly, by the time I could conduct these experiments (when I get to university), there will be more known types of repressors to switch off the DNA and this area of science will have move toward actual clinical trials.

Citations

Citations

Imperial College London. (2019). Genetic “Switch” Helps Breast Cancer Spread. Available here: https://www.technologynetworks.com/cancer-research/news/genetic-switch-helps-breast-cancer-spread-319975  accessed Sunday Feb 7 2021

 

NCI staff. (2020). Cancer Cells Hijack Gene “On Switches” To Drive Tumor Growth. Available here: https://www.cancer.gov/news-events/cancer-currents-blog/2020/glioblastoma-egfr-dna-circles accessed Sunday Feb 7 2021

 

Catharine Paddock. (2018). This 'genetic switch' could help to fight cancer. Available here:https://www.medicalnewstoday.com/articles/321646

 

Whitney Clavin. (2017). Taking a Closer Look at Genetic Switches in Cancer. Available here: https://www.caltech.edu/about/news/taking-closer-look-genetic-switches-cancer-72197

 

Dana Faber publishing. (2021). Scientists create ON-OFF switches to control CAR T cell activity. Available here:

https://www.dana-farber.org/newsroom/news-releases/2021/scientists-create-on-off-switches-to-control-car-t-cell-activity/

 

Ian Demsky. (2020) Turning On the “Off Switch” in Cancer Cells. Available here: https://labblog.uofmhealth.org/lab-report/turning-on-off-switch-cancer-cells

 

Helen Santoro. (2018). Study Identifies link between DNA-protein binding, cancer onset. Available here: https://med.stanford.edu/news/all-news/2018/10/study-identifies-link-between-dna-protein-binding-cancer-onset.html

 

WebMD (2020) Top Foods High in Tryptophan. Available here https://www.webmd.com/diet/foods-high-in-tryptophan#1

 

Canadian cancer society. (2016) Cancer Statistics at a Glance. Available here:https://www.cancer.ca/en/cancer-information/cancer-101/cancer-statistics-at-a-glance/?region=on#:~:text=Nearly%201%20in%202%20Canadians,expected%20to%20die%20from%20cancer

 

Jim Kozubek. (2016). What Gene Therapy Needs Now: A Good Off Switch. Available here:https://www.scientificamerican.com/article/what-gene-therapy-needs-now-a-good-off-switch/

 

Professor Dave Explains. (2017). Regulation of Gene Expression: Operons, Epigenetics, and Transcription Factors. available here: https://www.youtube.com/watch?v=J9jhg90A7Lw 

 

Acknowledgement

Thank you to my teachers and parents who supported this work.