Cancer Stem Cells: What They Are and How to Stop a Cancer Recurrence

Cancer and recurrence are two of the most frightful phrases someone may hear in relation to themselves or a loved one. Patients frequently inquire, “Why has this cancer returned?,” or, alternatively, “How do I prevent this cancer from returning?” The cancer stem cells, often known as “cancer seeds,” are what cause cancer to return. The ability to endlessly replicate itself, which also distinguishes normal stem cells, is one of the characteristics of all malignancies.

What Stem Cells are

A distinct population of cells in our body are called stem cells. They are unique for a number of reasons. They are eternal and produce every type of cell in our body. They do not perform any specific tasks, such as the contraction of heart muscles or the processing of light by retinal cells. Instead, they are intended to learn how to create differentiated cells, which are cells that are capable of doing certain tasks. Normally, when cells divide, they produce two identical cells. But when stem cells divide, they produce two distinct cells: one that stays a stem cell and increases the stem cell population, and a daughter cell that develops into a functional cell.

Stem cells come in a variety of forms, including:

Embryonic Stem cells

The sort of stem cells that have generated so much media attention and ethical discussion are embryonic stem cells. A blastocyst, which develops four to five days after conception and a few days before implantation, contains embryonic stem cells. The embryonic stem cells start to differentiate as soon as the blastocyst implants. Because embryonic stem cells are pluripotent, they can and do develop into virtually every type of cell in the body.

Adult Stem Cells

Adult stem cells are immortal and undifferentiated (they don’t form a definite role), just like embryonic stem cells. When they divide, they create a daughter cell that develops into a functioning cell, which will replace dead cells and repair damaged tissue, as well as another stem cell (self-regenerative). Adult stem cells, also known as somatic stem cells, are present in both children and adults. These stem cells cannot differentiate into a differentiated daughter that can become any cell type, as opposed to embryonic stem cells, which can only differentiate into a small number of functional cells. Our bodies include a small number of these stem cells that act as a repair system to replace damaged older cells with new, healthy organs, muscle, bone, nerve, and blood cells.

How long have cancer stem cells been studied?

Cancer’s capacity to spread to far-off areas has, to some extent, been viewed as a seed. When Steven Paget presented his “seed and soil” theory, this understanding was established. However, a number of investigations from Park and colleagues in the early 1970s discovered that some leukemic cells could re-produce a tumor while others could not. Two experiments conducted in 1997—one by Blair and the other by Bonnet and Dick—clearly identified cancer stem cells in a line of AML cells. According to this research, some leukemic cells possessed distinctive proteins on their surface. These cells routinely formed tumors that were identical to the original tumor when they were isolated. Both in cell cultures and when injected into trained immune-deficient animals, they were able to “create” new tumors.

Since the publication of these data, researchers have discovered correlated cancer stem cells in solid tumors, such as those of the brain, breast, lung, melanoma, prostate, pancreatic, colon, gastric, and lung, among others. It is critical to understand that differentiated cancer cells cannot form a new tumor, much like how only an apple seed can create a new apple tree and not an apple leaf.

What is the origin of cancer stem cells?

Healthy somatic stem cells that have acquired genetic alterations to become malignant give rise to cancer stem cells. In some ways, they are perfectly positioned to do so because the self-renewal system is already running in them. Somatic stem cells also have a considerably greater chance of developing mutations since they live a lifetime longer than more mature cells, which only survive for a brief time. We have long believed that the transition from stem cell to differentiated cell is one-way. However, we are discovering that a differentiated cell can actually de-differentiate and turn more stem-like under specific circumstances. Not only is this possible in our bodies, but scientists have also done this successfully in lab conditions.

Radiation and chemotherapy’s impact on cancer stem cells

Radiation and chemotherapy operate by targeting flaws in quickly dividing cells. This explains some of the more severe adverse effects of radiation, including reduced blood counts, nausea, and hair loss. This is so because the regular, healthy cells that make up our hair, digestive system, and blood marrow divide quickly and are thus more susceptible to the side effects of chemotherapy or radiation. Cancer stem cells, like all stem cells, do not, however, divide quickly; in fact, they divide considerably more slowly than any other form of cell. They become resistant to radiation and chemotherapy as a result.

Cancer stem cells not only divide too slowly to be harmed by chemotherapy and radiation, but they also retain a greater number of cellular systems capable of coping with the chemical side effects of these therapies, which increases their ability for survival. Additionally, it allows them the capacity to adjust to the therapy and develop medication resistance. Even the daughter’s fully differentiated cancer cells become resistant to therapy when these drug-resistant stem cells repopulate a tumor.

Additionally, the de-dedifferentiation pathways are activated by radiation and chemotherapy damage, which results in the regression we previously discussed. We eventually produce new cancer stem cells, which are typically more aggressive due to additional mutations. Both of these therapies will also cause a process known as EMT, or epithelial to mesenchymal transition. This promotes cells to change from epithelial cells, which are connected and remain in one location, to mesenchymal cells, which are separate from other cells and have an ideal shape for mobility.  Essentially, this is just another way of saying that these cells are ready to metastasize. The tumor can shrink if we simply treat the quickly dividing, differentiated cancer cells. But the seeds are still there, ready to sprout another, frequently more aggressive tumor.

Despite the information above, I want to be clear that chemotherapy does play a part in today’s cancer treatment. Just change the way we think about it. Chemotherapy typically doesn’t cure cancer since it can’t target cancer stem cells. However, it frequently causes tumors to shrink.

Recall the “seed and terrain” theory of cancer cells proposed by Paget. I prefer to compare the human body to a garden. Therefore, the question is whether the soil is ready to support healthy cells or to promote cancer cells. The terrain is essentially like this. Different chemical mediators are released by cancer cells to improve the conditions for the growth of cancer cells. Occasionally, it’s vital to remove the tumor’s bulk, therefore ignore those messages.

DO any conventional therapies address cancer stem cells?

Yes, a few is the quick answer. Keep in mind that in those initial studies conducted in 1997, the researchers discovered distinct proteins on the cell surfaces of the leukemic cancer stem cells. Imagine them as little hats that are exclusive to cancer stem cells. It turns out that these are the caps that all cancer stem cells wear. Even better, depending on the type of cancer cell, these caps may look slightly different. The fact that these surface proteins are the beginning of complex signaling cascades that are specific to stem cells is the best news, though. With healthy stem cells, these signaling pathways are frequently observed during embryonic development. Humorous names for them include hedgehog, notch, twist, and many more. There are numerous options for therapeutic intervention along these signaling pathways.

Vismodegib, which is used to treat locally invasive or metastatic basal cell carcinoma, is one of the earliest of these medications. The history of how this medicine came to be is intriguing. There were unexplained intermittent outbreaks of cyclopic lambs, or lambs born with only one eye, in the 1950s. This was methodically linked to the early-pregnancy grazing of sheep on Veratrum californicum, or corn lily. This resulted in the identification of the substance causing this birth abnormality, the steroid alkaloid cyclopamine. Over thirty years of research later, it was discovered that cyclopamine interfered with the hedgehog signaling system, which is found in stem cells during the early stages of embryonic development. Based on cyclopamine’s capacity to block the hedgehog signaling pathway, vismodegib was developed.

Another prominent medication that targets breast cancer stem cells is Herceptin, which is used to treat Her2 positive breast cancer. Her2, a protein on the surface of cells, functions as a growth factor receptor. Prior to the development of Herceptin (Trastuzumab), cancer cells that expressed high levels of the Her2 protein receptor were aggressive and challenging to treat, which makes sense given that growth factors hasten the growth of organisms. But now that Herceptin is available, finding a positive Her2 marker is good news because Herceptin kills cancer stem cells as well as differentiated cancer cells.

Herbal Allies

The fact that pharmacological medicines frequently have potent negative side effects makes using them to treat cancer stem cells difficult. For instance, in the vismodegib research from 2017 that we previously discussed, more than half of the individuals stopped taking the medication because of unpleasant side effects. Herbs can help with this. Numerous studies have demonstrated the beneficial effects of herbs on cancer stem cells. Curcumin, Resveratrol, Green tea, and Quercetin are the most frequently mentioned. Boswellia, Holy Basil, Honokiol, Milk Thistle, Ginseng, and numerous other herbs come next.

Recall how earlier we discussed signaling cascades? What does that even mean? In our bodies, a signaling cascade functions like a crazy Rube Goldberg machine where one protein changes another, which changes something else, ultimately altering how our DNA is processed. Returning to vismodegib, let’s discuss how it affects the Hedgehog signaling cascade. Notably, Curcumin, Resveratrol, Quercetin, and Green Tea all share this property. Drugs only strongly affect one signaling cascade, which frequently results in negative side effects. Herbs, on the other hand, frequently have a milder impact on a variety of signaling cascades, which results in less side effects.

One (or more) of three issues exist in cancers: the accelerator, or growth and division, is pressed too hard; the brakes, or inhibitors, aren’t functioning; or the signal to stop, or immortality, isn’t transmitted. Herbs are frequently used to target specific cancer stem cell pathways, such as hedgehog, notch, twist, etc., as well as to ease up on the growth accelerator and tighten the brakes. Our top four have outstanding anti-inflammatory, anti-irregular angiogenesis (new blood vessels growing to feed a tumor) inhibitory, anti-cancer cell stemness, anti-cancer cell death, and anti-metastatic efficacy properties.

Intervention with Nutrition

Nutrition also plays a significant part in influencing cancer stem cells in a favorable way, in addition to herbs. There is excellent research on soy’s genistein, honey’s and propolis’ chrysin, and broccoli’s and especially broccoli sprouts’ sulforaphane. Flavones, anthocyanins, and other phytochemicals from fruits and vegetables have long been known to protect and fight cancer.

Autophagy and Apoptosis 

The final topic I want to briefly discuss is autophagy and apoptosis. Our bodies are built to know when our proteins and cells need to be recycled or destroyed due to damage. In essence, autophagy and apoptosis are processes by which our systems neatly tie up damaged proteins (autophagy) and even whole cells (apoptosis) into bundles that may either be broken down and utilized for parts or removed. Both cancer stem cells and cancer cells inhibit these processes. It turns out that essentially restarting this process is an efficient strategy to combat cancer stem cells.  Numerous of the herbs and nutrients we discussed, including curcumin, green tea, resveratrol, and sulforaphane, also accomplish this. However, fasting is yet another effective strategy to promote apoptosis and autophagy. It has been demonstrated that 24-hour fasts and intermittent fasting, which lengthens the time between meals, both promote autophagy and apoptosis.

Cancer Stem Cells

A tumor was once thought to be homogeneous, made up of only one type of cell type that had continually grown. Currently, it is known that at least two of the cell types seen in tumors are cancer stem cells (CSC) and fully-grown cancer cells. All of the characteristics that spring to mind when we think of cancer cells are present in the differentiated cancer cells, including rapid growth, rapid division, abnormal cell shape, and involvement in the development of an inflammatory milieu that supports the disease.  Cancer stem cells resemble both somatic and embryonic cancer stem cells in many ways. They also self-renew, are immortal, and give rise to daughter cells that can develop into tumor cells. CSCs divide much more slowly than conventional cancer cells, and they also keep more cellular machinery in place. Drug resistance, metastasis, recurrence, and tumor genesis are all caused by cancer stem cells.