Written by: Lily Song

Cancer stem cells (CSC) are self-renewing cells identified in liquid and solid cancers. Today, Cancer stem cell (CSC) targeting for cancer therapy is considered an interesting area of current medical research. Understanding characteristics of CSCs and their signals would enable the development of more compatible, therapeutic approaches for targeting these cells. Examples of these characteristics include their precise location within a tumor, ways of targeting them, the proportion of CSC subpopulation in a given tumor, the relevance of CSCs to clinical outcome, and the origin of CSCs. Overall, by better understanding how to identify CSC’s, researchers can more effectively use CSC targeting in anti-cancer therapies.

CSC Targeting for Cancer Therapy 

Cancer stem cells (CSC) are self-renewing cells capable of differentiation and tumorigenicity, both of which are identified in liquid tumors and solid tumors. Liquid tumors are cancers present in body fluids (the blood and bone marrow) and solid cancers are cancers found in the lung, breast, prostate, colon and rectum, bladder. Solid cancers are not present in large enough numbers in body fluids to be detected with a blood test. Tumorigenicity is defined as the ability of cultured cells to give rise to benign or malignant progressively growing tumors. These stem cells have the ability to divide and expand the cancer stem cell pool and differentiate into the heterogeneous non tumorigenic cancer cells. They have been found in solid tumors and malignancies of the hematopoietic region (peripheral blood and the bone marrow), within tumor niches that bear enriched, functioning potential to drive cancer growth. Their tumorigenic activity has been attested in several cancers, including brain, liver, lung, colon, ovarian, breast, prostate, head and neck and bladder cancers. CSCs are reported to be responsible for sustained long‐term tumor growth, metastasis, and recurrence of cancer even after conventional cancer treatments such as radiation and chemotherapy. Overall, CSC’s are hidden in multiple areas, including liquid and solid tumors. However, with proper identification, they most definitely can be found.

Identification of CSCs

Researchers believe that an effective way to keep a tumor from relapsing and expanding is to target both CSCs and non-CSCs. They can be targeted through immunotherapy, hormone therapy, (mi)siRNA delivery, and gene knockout therapy. CSCs share several similarities with normal stem cells such as property, phenotype, and function. Therefore, they must be targeted based on their unique markers and their preferential expression of antigens, or foreign substances that cause your immune system to produce antibodies against it. They also share several other defining features with normal stem cells, including relative quiescence (inactivity), active DNA repair systems, aggressive proliferation, and drug resistance. CSCs are also highly plastic and are hidden deep within tumors, which hinders easy identification and eradication. Identification is generally based on cell surface marker expression: CD24, CD26, CD44, CD133, CD166, aldehyde dehydrogenase (ALDH) and Ep‐CAM (also called CD326 or epithelial‐specific antigen/ESA) are examples of CSC‐specific surface markers. Sometimes, even CSCs and normal stem cells have the same cell surface markers. Some markers are inherited from CSCs in association with their tumorigenic potential, which are called “oncogene inherited” markers. Tumors with active mutations of the RAS pathway often harbor the oncogenic drivers, which are mutations that are responsible for both the initiation and maintenance of cancer. An example of such a marker is the mesenchymal-epithelial transition (MET). The widespread expression of such markers in tumors can be interpreted as the expansion and metastasis of CSCs. Unfortunately, identifying CSC markers may not always result in a true CSC cell, which then becomes a specificity and sensitivity issue. Other ways to identify CSCs are through flow cytometry and immunostaining. Some of these methods will work for some cells, while others will not. 

Killing CSCs during cancer therapy is an essential part of antitumor therapies, as even a single CSC can be capable of reconstituting an entire tumor. Despite this, CSC targeting is still a novel anti-cancer discovery, and researchers believe that, with more research, will be a promising anti-cancer practice. In the future, understanding and recognizing the key characteristics of CSC’s, such as its precise location within a tumor, ways of targeting them, the proportion of CSC subpopulation in a given tumor, the relevance of CSCs to clinical outcome, and its origin, can lead to optimistic findings. 

Works Cited

Najafi M., Farhood B., & Mortezaee K. (2019). Cancer stem cells (CSCs) in cancer progression and therapy. Journal of Cellular Physiology, 234(6), 8381–8395. https://sites.imsa.edu:2178/10.1002/jcp.27740 

Bacakova L., Zarubova J., Travnickova M., Musilkova J., Pajorova J., Slepicka P., Kasalkova N. S., Svorcik V., Kolska Z., Motarjemi H., & Molitor M. (2018). Stem cells: their source, potency and use in regenerative therapies with focus on adipose-derived stem cells – a review. Biotechnology Advances, 36(4), 1111-1126. https://doi.org/10.1016/j.biotechadv.2018.03.011

Yu, Z., Pestell T. G., Lisanti M. P., & Pestell R. G. (2012). Cancer stem cells. The International Journal of Biochemistry & Cell Biology, 44(12), 2144–2151. https://doi.org/10.1016/j.biocel.2012.08.022