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Cancer Stem Cells and
Senescent Cancer Cells

Most cancer deaths caused by metastasis.

It is estimated that metastasis is responsible for about 90% of cancer deaths. This estimate has changed little in more than 50 years, says this study.

Most metastases caused by Cancer Stem Cells (CSCs).

CSCs have been shown in numerous cancer models to be involved in tumor development, cell proliferation, and metastatic dissemination, while possessing a capacity for sustained self-renewal. CSCs, which typically represent a small proportion of total cells of a given tumor, also exhibit resistance to chemotherapy and radiotherapy. Indeed, exposure to these treatments may promote “stemness” in nonstem cancer cells, which may explain why successful therapeutic reduction of tumor bulk will often fail to produce clinical improvement, says this 2016 study.

Senescent Cancer Cells are also responsible for metastasis.

Senescence is the process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing cell death.

According to this 2020 Review in Trends in Cancer, a significant number of commonly used cancer interventions have been associated with the induction of cellular senescence in either tumor or non-tumor cells and tissues.

Therapy-induced senescence can cause cancer metastasis and relapse and several adverse reactions to cancer treatments.

More about Senescent Cancer Cells


How can we target Cancer Stem Cells?

According to this 2020 study: Cancer stem cells (CSCs) contribute to the initiation, recurrence, and metastasis of cancer; however, there are still no drugs targeting CSCs in clinical application.

Natural Products Target Cancer Stem Cells

This scientific review says natural products, including those found in common foodstuffs have demonstrated the ability to modulate pathways responsible for Cancer Stem Cells function and inhibition.

Top Five
This 2020 study says: Certain phytochemicals, in particular
curcumin,
epigallocatechin-3-gallate (EGCG),
sulforaphane,
resveratrol and
genistein
have been shown to interfere with…CSC pathways…leading to elimination of CSCs.

In addition, the following targeted Cancer Stem Cells in lab studies
Ashwagandha (supplement)
B-carotene (supplement)
Bee Propolis (containing Caffeic Acid Phenethyl Ester (CAPE))
Delphinidin (Raspberries and Blueberries)
Falcarinol and falcarindiol (carrot and parsley)
Feverfew and Green Chirayta (plant extracts)
Ginger (spice)
Indole-3-Carbinol (I3C) (food supplement)
Ivermectin (river blindness treatment)
Lycopene (tomatoes)
Niclosamide (tapeworm treatment)
Parthenolide
Piperine (black pepper)
Silibinin (Milk Thistle seed extract)
Salinomycin (anti-biotic drug)
Ursolic acid (food supplement)
Vitamin D (sunshine)

How can we target Senescent Cancer Cells?

Senolytics are a class of drugs that selectively clear senescent cells (SC). Studies have identified the following compounds as Senolytics:

  • Curcumin (natural plant compound)
  • Tocotrienols (a type of vitamin E nutrient)
  • Piperlongumine (a natural alkaloid)
  • Nicotinamide riboside (a micronutrient)
  • Berberine (a plant extract)
  • Dasatinib (chemo drug) and Quercetin (a plant pigment) – used in combination.
  • Danazol (androgenic hormone)
  • Foxo4 (protein) inhibitors
  • HSP90 (protein) inhibitors
  • Navitoclax (ABT263) (anti-cancer drug)
  • Phloretin (a crystalline substance)
  • Selective BCL-XL inhibitors A1331852 and A1155463 ( targeted therapies)

Sources: Study, Study, 2019 Review


More about Cancer Stem Cells

Cancer stem cells (CSCs), also called “tumor-initiating cells” or “cancer-initiating cells”, are a small subpopulation of self-renewing malignant and oncogenic cells that drive tumor initiation and progression. CSCs play pivotal roles in tumor initiation, progression, cell death resistance, therapy resistance, and tumor recurrence following treatment and remission. Exposure to chemo – or radiotherapy may also promote “stemness” in nonstem cancer cells – Ahmad R. Safa, in Oncogenomics, 2019

Image credit: Bio-Connect

Cardiff University website says: This type of stem cell represents a small proportion of the types of cell found in a tumour, and can replicate tumour cells, causing tumours to grow and spread. Cancer stem cells are considered resistant to drug and radiotherapy treatments, and therefore can be left behind after the course of cancer treatment comes to an end, allowing the tumour to regrow and spread around the body.

Cancer stem cells (CSCs), which comprise a small fraction of cancer cells, are believed to constitute the origin of most human tumors. … Many studies also suggest that CSCs serve as the basis of metastases, says this study.

The Stem Cell Theory of Cancer

… many new anti-cancer 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 a vexing resistance to the previously used therapy). An analogy would be a weeding technique that is evaluated based on how low it can chop the weed stalks—but no matter how low the weeks are cut, if the roots aren’t taken out, the weeds will just grow back.
Source: Stanford Medicine

CSCs have been identified in over 20 cancer types to date, but it remains unknown how to target and eliminate CSCs in vivo, says this 2020 study

Conventional Treatments do not kill Cancer Stem Cells

There is extensive preclinical evidence in animal models that nearly all types of cancer treatments, from surgery to chemotherapy and targeted therapy, can stimulate tumor spread, states this study.

This study says: Resistance to chemotherapy and radiotherapy has been observed repeatedly in CSCs. If CSCs are resistant to treatment, and treatment to destroy cancer cells succeeds primarily in killing only nonstem cancer cells, it may explain the phenomenon of successful therapeutic tumor shrinkage without a corresponding improvement in patient survival.

Alcohol progresses existing cancers

This study says: It appears that alcohol exposure not only promotes carcinogenesis but also enhances the progression and aggressiveness of existing cancers.

Available evidence indicates that alcohol increases Cancer Stem Cell population, and therefore may promote aggressiveness, recurrence, and therapy resistance of cancers.

Xu, M.; Luo, J. Alcohol and Cancer Stem Cells. Cancers 2017, 9, 158. https://doi.org/10.3390/cancers9110158.


More about Senescent Cancer Cells

Senescence is generally regarded as a tumour suppressive process, both by preventing cancer cell proliferation and suppressing malignant progression from pre-malignant to malignant disease. It may also be a key effector mechanism of many types of anticancer therapies, such as chemotherapy, radiotherapy, and endocrine therapies, both directly and via bioactive molecules released by senescent cells that may stimulate an immune response. However, senescence may contribute to reduced patient resilience to cancer therapies and may provide a pathway for disease recurrence after cancer therapy. (read study)

While senescence can prevent tumour growth (cancer is characterised by unchecked cell proliferation), in the last few years the presence of senescent cells after cancer therapies has also been associated with relapse – source

This study, published in the Journal of the National Cancer Institute puts it this way: Treatment-induced Senescence in tumor cells induces several features that may be beneficial to the treatment of cancer. Importantly, senescence stimulates a persistent terminal growth arrest…

Cell division is important for normal growth and repair. Senescent cells, sometimes called ‘zombie cells’, lose that capacity and enter an enduring growth arrest. While senescence can prevent tumour growth (cancer is characterised by unchecked cell proliferation), in the last few years the presence of senescent cells after cancer therapies has also been associated with relapse. – source

Senescent tumor cells … establish a shield surrounding the cancer cells and build a supportive tumor microenvironment. Therefore, eliminating senescent tumor cells…is proposed as a new strategy for inhibiting cancer progression through blocking the adverse effects of senescent tumor cells and enhancing the efficacy of cancer immunotherapy. – source

This study concluded: Overall, cancer cell senescence is a Jekyll and Hyde phenomenon with both beneficial and detrimental implications. Despite a primary and immediate tumor-suppressive role against cancer development, the long-term consequences of senescent cancer cells are potentially deleterious.


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