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Summary -
This article talks about how stem cells can be used in cancer treatment, their advantage over conventional methods and the various strategies employed to utilize stem cells in treating cancer.
Cancer is the second leading cause of death all across the world (1). The mere mention of this would make your gut slightly churn. Innumerable lives have vanished, countless lost hope and succumbed to this deadly disease. Evidence has shown that cancer has existed since the Jurassic era and affected even the dinosaurs (2). Since then, the struggle against cancer has continued. Over the years, scientists have been digging deeper and developing treatment methods to alleviate human suffering and deal with this menace. Most used treatments include surgery, chemotherapy, radiotherapy and immunotherapy. Surgery removes the solid tumours, chemotherapy uses drugs to eliminate tumours, radiotherapy damages cancer cell DNA to eradicate tumours, and immunotherapy utilizes antibodies or inhibitors to treat cancer.
These are all effective against benign tumours which cannot invade neighbouring tissues. However, metastatic cancer cells, which have the ability to spread throughout the body (metastasize), are difficult to eliminate using conventional methods, and recurrence is prevalent. Resistance to chemotherapeutic drugs, the expensive targeting procedures and toxicity to the normal tissues are some of the issues complicating cancer treatment. As a result, scientists have been looking for alternatives to curb this menace. Over the past few decades, leveraging stem cells in cancer treatment has gained attention.
Before we delve deeper into the how-and-why, let's talk about these cells. Stem cells, primarily found in the bone marrow, can renew themselves and form clonal cell populations and differentiate into many types of cells. Stem cells furthermore have antitumour and migratory properties. They express cytokines and growth factors that regulate immune pathways and escape host immune response. In addition, they can interact with cancer cells and exert antitumour effects. These supercells have been used to treat diseases by transplanting them into the patient's body, and many novel therapies are being developed.
These supercells are used in various therapies to treat cancer. For instance, in enzyme-based treatments, stem cells are localized to tumour tissues by utilizing their homing property, the ability to respond to chemical gradients in blood and lodge within specific tissues (3), (4). Then the enzyme converts the prodrug into a cytotoxic product which damages the tumour cells. Stem cells can also function as drug factories and secrete antitumor agents for long periods, dealing with short drug half-life. They can also be used as nanoparticle delivery agents to deliver chemotherapeutic drug-carrying nanoparticles to the tumour site causing the reduction in uptake and degradation of nanoparticles by the body's phagocytes (3).
Stem cells transplant is also an option in therapy for cancers that affect the bone marrow, such as leukaemia, lymphoma and multiple myeloma. In an autologous transplant, stem cells from the patient's blood or bone marrow are used, and in an allogeneic transplant, stem cells are received from a donor. The high dose of chemotherapy or radiation to eliminate cancer cells also eliminates the blood-producing cells left in the bone marrow. Then, the collected stem cells are released back into the bloodstream, eventually reaching the bone marrow because of their homing process. It mainly involves interaction between stem cell CXCR4 receptor and SDF-1 secreted by cells lining the bone marrow. Since such high doses cause the bone marrow to stop producing blood cells for a long time, this ensures that the body starts producing healthy cancer-free blood cells after treatment (4).
Stem cells release paracrine factors such as exosomes which can target tumour cells where they get internalized into cells and release targeting cargo. Stem cells are also being used to produce chimeric antigen receptor (CAR) T-cells in cancer immunotherapy. These T cells have been modified by expressing chimeric antigen receptors on their surface, giving them the ability to chase down and eliminate cancer cells. They remain in the body as a defence even after cancer is gone. Think of these cells as patrolling police in your body, ready to strike cancer cells the moment they encounter them. Numerous clinical trials are investigating CAR T cell therapies for various cancer types (5). Treatment using cancer stem cells vaccines is also highly encouraging. This will help the immune system recognize many different types of tumour proteins and stimulate an immune response against various kinds of cancer.
As a weapon in the battle against cancer, stem cells have shown great potential that cannot be sidelined and is highly expected to open new doors for cancer treatment.
References
1. An Update on Cancer Deaths in the United States. (2021). Retrieved 14 January 2022, from https://www.cdc.gov/cancer/dcpc/research/update-on-cancer-deaths/index.htm#:~:text=Cancer%20was%20the%20second%20leading,females%20and%20315%2C876%20among%20males.
2. Ekhtiari, S., Chiba, K., Popovic, S., Crowther, R., Wohl, G., & Kin On Wong, A. et al. (2020). First case of osteosarcoma in a dinosaur: a multimodal diagnosis. The Lancet Oncology, 21(8), 1021-1022. doi: 10.1016/s1470-2045(20)30171-6
3. Chu, D., Nguyen, T., Tien, N., Tran, D., Jeong, J., & Anh, P. et al. (2020). Recent Progress of Stem Cell Therapy in Cancer Treatment: Molecular Mechanisms and Potential Applications. Cells, 9(3), 563. doi: 10.3390/cells9030563
4. Zhang, C., Huang, T., Wu, B., He, W., & Liu, D. (2017). Stem cells in cancer therapy: opportunities and challenges. Oncotarget, 8(43), 75756-75766. doi: 10.18632/oncotarget.20798
5. Masoumi, J., Jafarzadeh, A., Abdolalizadeh, J., Khan, H., Philippe, J., Mirzaei, H., & Mirzaei, H. (2021). Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects. Acta Pharmaceutica Sinica B, 11(7), 1721-1739. doi: 10.1016/j.apsb.2020.12.015
About the Author
Himanshi Yadav has recently completed Masters in Zoology with a specialization in Molecular Endocrinology and Reproduction from Miranda House, University of Delhi. She aspires to research and delve deep into Neuroscience and Cancer Biology. Her other fields of interest include Public health. She is keen on broadening the horizons of how science is being communicated and actively advocates for gender equality in STEM, inclusivity, and mental health awareness.
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