They influence how a tumor grows

By Julia Knox 

 Medically reviewed by Doru Paul, MD

Cancer stem cells are a small subpopulation of cells found within tumors that are tumorigenic, meaning they can create a cancerous tumor.1 Self-renewal and the ability to differentiate into diverse cell types are hallmark features of cancer stem cells. They can reproduce themselves and sustain cancer in the body. They are therefore hypothesized to be the primary driver of cancer growth and metastasis.2 This is called the stem cell theory of cancer. Effective cancer treatment then must target and attack these cells. Doing so can improve the chances of cancer remission.

Cancer stem cells have been identified in brain, breast, colon, ovarian, pancreatic, and prostate tumors, as well as in melanoma, multiple myeloma, nonmelanoma skin cancer, and leukemia.1

Cancer stem cell research is ongoing, and new studies are emerging frequently.

What Are Stem Cells?

Stem cells are undifferentiated (or only partly differentiated) human cells that can turn into different types of cells in the body, from nerve cells (neurons) to brain cells. They can also fix damaged tissues. They must possess two major qualities: self-renewal and the capacity to differentiate. Stem cell-based therapies are also being studied to treat serious illnesses such as paralysis and Alzheimer's disease.3

There are two types of stem cells: embryonic and adult stem cells. Embryonic stem cells come from unused embryos and are created from an in vitro fertilization process. They are pluripotent, meaning they can turn into more than one cell type.3 Within adult stem cells, there are two different types: one type comes from fully developed tissues such as the brain, skin, and bone marrow, and the other is induced pluripotent stem cells, which have been changed in the lab to be more like embryonic stem cells.

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What Are Cancer Stem Cells?

The stem cell theory of cancer hypothesizes that cancer stem cells are thought to drive tumor initiation and may be responsible for therapeutic resistance and cancer recurrence.4

Like many areas of biomedical research, cancer stem cells are an evolving field of study. Multiple studies have indicated that insufficient evidence exists to confirm the existence of cancer stem cells. A review of 1,000 Web of Science publications revealed that only 49% supported the cancer stem cell hypothesis.5

Cell surface markers can be used to identify cancer stem cells, as has been done in research that supports the hypothesis that these stem cells do not respond to traditional therapies such as chemotherapy. This research also supports the idea that cancer stem cells are the source of cancer metastasis.1

Like all stem cells, cancer cells must have the following characteristics:

• Self-renewal: When stem cells divide into more stem cells, this process is referred to as cell renewal.

• Cell differentiation: Cell differentiation is when a cell changes from a less differentiated to a more differentiated cell type.

Role in Cancer Growth

Cancer stem cells use specific signaling pathways.6 It is hypothesized that cancer stem cells can also act as a reservoir of cancer cells, which may cause a relapse after surgery, radiation, or chemotherapy has eliminated all observable signs of cancer.7 Targeting these cells would thus highly improve the chances of a patient's remission if cancer stem cells are the origin of the tumor.

Resistance to Therapy

Cancer stem cells have the capacity to change into more specialized cell types, so they can potentially lead to tumor cell heterogeneity.8 Due to this quality, they are cited as a major factor of chemoresistance.9 Their highly resistant nature can lead to tumors metastasizing and tumor regrowth.10 As such, the developing research on cancer stem cells could dramatically change the prognosis of multiple cancer types.

Also, many new anticancer therapies are evaluated based on their ability to shrink tumors, but if the therapies are not killing the cancer stem cells, the tumor will soon grow back, often with resistance to the previously used therapy.7

Importance of Cancer Stem Cell Research

Cancer stem cell research is critical because it addresses the potential root cause of cancer proliferation and can lead to the development of more effective and safer treatments. Treatments targeting cancer stem cells will likely have fewer side effects compared with existing options because they will leave other kinds of cells untouched.11

Understanding these cells can also help modify current treatments for maximum effect. Research has shown that cancer stem cells are resistant to the ionizing radiation used to treat cancer. Understanding this resistance may in the future help researchers find compounds that undermine this process and make cancer stem cells vulnerable to radiation damage.7

Sources

Yu Z, Pestell TG, Lisanti MP, Pestell RG. Cancer stem cells. Int J Biochem Cell Biol. 2012 Dec;44(12):2144-51. doi: 10.1016/j.biocel.2012.08.022

Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci. 2018 Mar 6;25(1):20. doi: 10.1186/s12929-018-0426-4

Stanford Children's Health. What are stem cells?

Walcher L, Kistenmacher AK, Suo H, Kitte R, Dluczek S, Strauß A, Blaudszun AR, Yevsa T, Fricke S, Kossatz-Boehlert U. Cancer stem cells-origins and biomarkers: perspectives for targeted personalized therapies. Front Immunol. 2020 Aug 7;11:1280. doi: 10.3389/fimmu.2020.01280

Bartram I, Jeschke JM. Do cancer stem cells exist? A pilot study combining a systematic review with the hierarchy-of-hypotheses approach. PLoS One. 2019 Dec 13;14(12):e0225898. doi: 10.1371/journal.pone.0225898

Dawood S, Austin L, Cristofanilli M. Cancer stem cells: implications for cancer therapy. Oncology (Williston Park). 2014;28(12):1101-1110.

Stanford Medicine. The stem cell theory of cancer.

Nassar D, Blanpain C. Cancer stem cells: basic concepts and therapeutic implications. Annu Rev Pathol. 2016;11:47-76. doi:10.1146/annurev-pathol-012615-044438

Barbato L, Bocchetti M, Di Biase A, Regad T. Cancer stem cells and targeting strategies. Cells. 2019;8(8):926. doi:10.3390/cells8080926

Ayob AZ, Ramasamy TS. Cancer stem cells as key drivers of tumour progression. J Biomed Sci. 2018;25(1):20. doi.org/10.1186/s12929-018-0426-4

Stanford Medicine. What CSCs mean for cancer treatment.