Out of the innumerable articles written to commemorate the 50th anniversary of the National Cancer Act only a tiny minority mentioned one of the signal achievements of that effort: the discovery of cancer stem cells. But scientists from Harvard and Wayne State Universities got it right:

The year 2021 marks the 50th anniversary of the National Cancer Act, signed by President Nixon, which declared a national “war on cancer.” Powered by enormous financial support, this past half-century has witnessed remarkable progress in understanding the individual molecular mechanisms of cancer, primarily through the characterization of cancer genes and the phenotypes associated with their pathways.¹

Key among these findings has been the identification of the markers of “stemness” in a special class of cancer cells known as “cancer stem cells” (CSCs). These are defined as “a subpopulation of tumor cells that can drive tumor initiation and can cause relapses.”²

The existence of CSCs was strongly suspected in the 19th century by the likes of Rudolph Virchow, Julius F. Cohnheim, and John Beard, D.Sc. These European professors theorized that the ultimate origin of cancer could be found in primitive cells that were leftovers from the period of embryo formation. Modern scholars have written:

More than 150 years ago, Rudolf Virchow and Julius Cohnheim proposed the intriguing hypothesis that cancer may develop from embryonic cell remnants that remain in the developing organs following embryogenesis. This hypothesis, known as the “embryonic rest hypothesis of cancer development,” was popular in textbooks of pathology in the nineteenth and twentieth centuries.³

Even today, certain cancers are routinely recognized as of embryonal origin. This includes neuroblastomas, i.e., cancers that originate in neuroblast cells, usually of the adrenal gland, which are defined as “undifferentiated precursors of the central nervous system (CNS).”⁴

In all mammals, the maturation of neuroblasts is completed shortly after birth. In rare cases, however, neuroblasts fail to complete their development and become malignant.” According to one dictionary, “neuroblastomas are tumors that can arise during the malignant degeneration of neuroblasts.”⁵

Professor John Beard (1858-1924) of the University of Edinburgh, took this one step further. He proposed that all cancers were not just derived from “embryonal rests,” as such remnants of earlier development were usually called but were identical to the trophoblastic cells of pregnancy. As we wrote in a special journal issue on Beard and Beard’s legacy:

Beard was the first to point to the parallels between cancer and the trophoblastic cells that envelop and nourish the embryo, characterizing cancer as ‘irresponsible trophoblast.’ He pointed out that the initiation of fetal pancreatic function coincided with a reduction in the invasiveness of trophoblast, which otherwise might progress to clinical cancer (ie, choriocarcinoma). Based on the above propositions, he recommended the therapeutic use of pancreatic enzymes in treating cancer and other diseases. This therapy created a worldwide controversy, and although rejected in his day, persists in the world of complementary and alternative medicine (CAM) today.⁶

I was thinking particularly of the work of Ernst T. Krebs, Jr. William B. Kelley, DDS, and Nicholas Gonzalez, MD, who wrote an entire book on the topic.⁷ In conventional medicine, this theory is widely rejected today and only has a few adherents in the world of CAM. One logical flaw in the argument is that, were it true, all cancers would conspicuously produce the hormones associated with pregnancy. In fact, only a few of them do.

But it remains true that the first diagnostic tests for cancer, alpha fetoprotein (AFP), carcinoembryonic antigen (CEA), and human chorionic gonadotropin (hCG), were all based on a recognition of some cancers’ embryonic origin. These developments (flawed as they were) did keep alive the idea of a class of primitive cells lurking within a much larger population of ordinary tumor cells. These early thinkers paved the way for our current understanding of “cancer stem cells.”

Indeed, Beard’s thinking on the origin of cancer has been hailed as a forerunner of the present-day theory of cancer stem cells. “Cancer arises from displaced trophoblast of activated germinal cells,” wrote Stewart Sell, MD, in his Stem Cell Handbook.⁸ In this book, Beard’s name followed that of the great Virchow and Cohnheim in anticipating today’s CSC theory. This was the first time that Beard’s name was linked to the concept of CSCs.

Cancer stem cells are now the subject of over 16,000 PubMed journal articles. The topic continues to fascinate an increasing number of researchers around the world. From a single article that first appeared in 1983, there are now almost 2,000 such articles per year, about five every day of the week. This field has come a long way since 1997 when Prof. John Dick, Ph.D., and his group at the University of Toronto isolated a population of primitive stem cells in acute myeloid leukemia (AML). Today, there is “accumulating evidence” in the scientific literature that cancer stem cells are in fact the “driving force behind tumor initiation, progression, metastasis, drug resistance, and recurrence”⁹

Think about that! Scientists have discovered a group of unique cells that are responsible for just about everything that makes cancer fearful. Besides initiation, progression, metastasis, drug resistance, and recurrence, what exactly do we have to fear from this disease? Without the presence of CSCs, cancer might simply be a benign growth, a “space-occupying lesion” that could be ablated or permanently removed by robotic surgery.

Yet very few cancer patients ever hear about this breakthrough finding. That is because drug-oriented medical oncologists are waiting for approval of the first anti-CSC drug to be announced by the Food and Drug Administration (FDA). Meanwhile, there are phytochemicals (or nutraceuticals) that are already known to kill cancer stem cells. It is just a question of figuring out how to give these in the most effective way.

A key paper that points the way to a natural control of CSCs was the outstanding contribution of Dwight L. McKee, MD, and Cord Naujokat, MD, PhD, called “The Big Five.”¹⁰ McKee is a retired American medical oncologist, and Naujokat is a senior researcher at the Institute of Immunology, University of Heidelberg (Germany). They brought together a vast amount of research on the use of foods and food-derived factors on CSCs, especially resveratrol, soy isoflavones, sulforaphane, curcumin, and EGCG (green tea).

Another big step in this direction was taken by Australian researcher Myfanwy Webb, PhD, and the medical oncologist, Craig Kukard, MD. Their excellent 2020 article in Integrative Cancer Therapies reviewed the use of natural therapies for triple negative breast cancer (TNBC), “aimed at targeting cancer cell vulnerabilities.”¹¹ The vulnerabilities in question are the markers of CSC. The substances found to counteract CSCs in TNBC turned out to be very similar to the “Big Five” in McKee and Naujokat’s article. In particular, these identified seven substances that were relevant to the destruction of CSCs: curcumin, burdock, garlic, fisetin, Korean ginseng, sulforaphane and quercetin. But although there are about a dozen and a half articles on the natural treatment of CSCs, much work still needs to be done. In the future, hopefully, each individual’s tumor cells will be studied for the presence of a dozen or so characteristic markers of CSCs, and then appropriate nutraceuticals will then be prescribed to counteract each of these. This is technologically possible at the present time.

However, although a scientific breakthrough is within our grasp, the political and economic barriers are more formidable. Such treatments inevitably run into what the former National Institutes of Health official, Wayne Jonas, MD, has called “the valley of death.” This is the fact that natural treatments cannot deliver the financial returns that would justify the expense of clinical trials. It will take concerted public pressure to get the NIH and other non-profits to sponsor research into the individualized treatment of cancer stem cells with natural, non-toxic agents. The effort will be great, but the payoff in terms of improved outcomes could be equally enormous.

References

1. Heng J, Heng HH. Genome Chaos, Information Creation, and Cancer Emergence: Searching for New Frameworks on the 50th Anniversary of the “War on Cancer”. Genes (Basel). 2021 Dec 31;13(1):101. doi: 10.3390/genes13010101. PMID: 35052441; PMCID: PMC8774498.
2. Walcher L, et al. Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies. Front Immunol. August 7, 2020.
3. Ratajczak MZ, et al. (2013) The Embryonic Rest Hypothesis of Cancer Development: 150 Years Later. In: Resende R., Ulrich H. (eds) Trends in Stem Cell Proliferation and Cancer Research. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6211-4_3, 2013.
4. Bradley and Daroff’s Neurology in Clinical Practice, 2-Volume Set, 8th Edition, Amsterdam; Elsevier, 2021.
5. TheFreeDictionary.com
6. Moss RW. The life and times of John Beard, DSc (1858-1924). Integr Cancer Ther. 2008 Dec;7(4):229-51.
7. Gonzalez, Nicholas and Isaacs, Linda L. The Trophoblast and the Origins of Cancer: One Solution to the Medical Enigma of our Time. New Spring Press, 2009.
8. Sell, Stewart. Stem Cell Handbook. Totowa, NJ: Humana Press; 2003)
9. Hager JC, Heppner GH. Breast cancer stem cells. Prog Clin Biol Res. 1983;132C:137-46. PMID: 6634769; Zhang X, Powell K, Li L. Breast Cancer Stem Cells: Biomarkers, Identification and Isolation Methods, Regulating Mechanisms, Cellular Origin, and Beyond. Cancers (Basel). 2020 Dec 14;12(12):3765. doi: 10.3390/cancers12123765. PMID: 33327542; PMCID: PMC7765014.
10. Naujokat C, McKee DL. The “Big Five” Phytochemicals Targeting Cancer Stem Cells: Curcumin, EGCG, Sulforaphane, Resveratrol and Genistein. Curr Med Chem. 2021;28(22):4321-4342.
11. Webb MJ, Kukard C. A Review of Natural Therapies Potentially Relevant in Triple Negative Breast Cancer Aimed at Targeting Cancer Cell Vulnerabilities. Integr Cancer Ther. 2020 Jan-Dec;19:1534735420975861.