Why Targeting Cancer Stem Cells is Crucial for Survival
Cancer stem cells are a critical yet often overlooked aspect of cancer treatment. This video explains the crucial role of cancer stem cells in disease initiation, progression, metastasis, and recurrence.
Continue on to the article below if you would rather read than watch a video.
What isn’t Your Doctor Telling You About Cancer Stem Cells
Patients that don’t target cancer stem cells are at an increased risk of developing metastatic cancer and suffering from disease recurrence. But this is not their fault. Most cancer clinics and hospitals do not speak of the existence of cancer stem cells to patients, nor offer any recommendations on how to potentially mitigate them. In this article, I will clearly summarize the role cancer stem cells play in disease initiation and progression, as well as ways they could be targeted.
In the early 1990s, a groundbreaking discovery was made that would change our understanding of cancer. Researchers at the University of Toronto, led by Dr. John Dick, were the first to identify cancer stem cells in human acute myeloid leukemia. They found that only a small subset of leukemia cells, could initiate leukemia when transplanted into mice. This suggested cancers may be driven by a rare population of stem-like cells.
Since then, cancer stem cells have been a major focus of cancer research worldwide. Prominent cancer research centers like the Harvard, Stanford, MIT, and others have made important discoveries showing that cancer stem cells exist in many solid tumors as well, including breast, brain, colon, pancreatic, lung and others. These cancer stem cells have unique properties that allow them to drive tumor growth, metastasis, recurrence, and treatment resistance. Let’s breakdown their impact on different disease stages.
Cancer initiation
Researchers now believe that cancer stem cells play a central role in initiating and sustaining tumor growth. Like normal stem cells, cancer stem cells can self-renew indefinitely and produce all the diverse cell types found in a tumor. Evidence suggests cancer stem cells may arise from normal stem cells or progenitor cells that have acquired oncogenic mutations. They make up only a small fraction of cells in a tumor, but continuously regenerate themselves and the bulk tumor cells. Eliminating the cancer stem cells is therefore thought to be crucial for truly curing a cancer.
Progressing to metastasis
Cancer stem cells have also been implicated as the source of cancer metastasis. They are able to migrate through the bloodstream and seed new tumors in distant organs. Cancer stem cells often have a mesenchymal phenotype and express genes that allow them to invade through extracellular matrix, enter and exit blood vessels, and initiate a new tumor in a foreign tissue microenvironment. Disseminated cancer stem cells can remain dormant for long periods before reactivating to form a metastatic tumor. The unique properties of cancer stem cells may explain why metastatic cancers are so difficult to treat.
Cancer stem cell role in recurrence
Even when a primary tumor is surgically removed or seemingly eliminated by chemotherapy or radiation, cancer stem cells left behind can drive recurrence of the cancer months or years later. Like a seed, a single surviving cancer stem cell can regenerate a whole new tumor. This may explain why cancers so often recur after periods of remission. Preventing recurrence likely requires targeting and eliminating the cancer stem cell population.
Unfortunately, standard treatments fail to target cancer stem cells. Conventional chemotherapy and radiation target rapidly dividing cells, but have limited effectiveness against cancer stem cells, which divide more slowly. Cancer stem cells also have high expression of drug efflux pumps, anti-apoptotic proteins, and efficient DNA repair mechanisms that make them more resistant to standard treatments. Additionally, the tumor microenvironment provides protective niches that shelter cancer stem cells from chemotherapy and radiation. The inability of these treatments to target cancer stem cells could be the reason why cancer centers are hesitant to discuss this obstacle with patients.
While standard cancer treatments like chemo and radiation seem unable to address cancer stem cells, there are many existing medications that have demonstrated the ability to destroy cancer stem cells. These repurposed drugs are existing medications, often generic and off-patent, have been safely used for other conditions but have shown promise in treating cancer by targeting cancer stem cells. Using repurposed drugs offers several advantages: they have a clear safety profile, are readily available, and are often more cost-effective than developing new drugs from scratch. Studies show dozens of existing medications that were observed to damage or destroy cancer stem cells, we will discuss three examples:
Chloroquine
Chloroquine, an antimalarial drug, has been found to target cancer stem cells through various mechanisms. It can inhibit autophagy, a process that cancer stem cells rely on for survival. Additionally, chloroquine has been shown to alter the Jak2-STAT3 pathway and DNMT1 expression, which are critical for cancer stem cell maintenance. In a study by Choi et al., chloroquine was found to eliminate cancer stem cells in triple-negative breast cancer. Clinical trials are ongoing to evaluate chloroquine's efficacy in targeting cancer stem cells in various cancer types, including glioblastoma and breast cancer.
Doxycycline
Doxycycline, an antibiotic, has been found to target cancer stem cells by inhibiting mitochondrial biogenesis. Cancer stem cells rely on enhanced mitochondrial function for their survival and proliferation. In a study by Zhang et al., doxycycline was found to inhibit the stem cell phenotype and epithelial-to-mesenchymal transition in cancer cells.
Mebendazole
Mebendazole, an anthelmintic drug used to treat parasitic infections, has shown anti-cancer stem cell properties. It has been found to inhibit multiple pathways critical for cancer stem cell survival, including the Hedgehog and Notch signaling pathways. In a study by Bai et al., mebendazole was found to inhibit brain tumor stem cells and enhance the efficacy of temozolomide, a standard chemotherapy drug for glioblastoma. Mebendazole's ability to target cancer stem cells and enhance the effectiveness of conventional therapies makes it a promising candidate for drug repurposing in cancer treatment.
Recap
Cancer stem cells have unique properties that indicate they play a critical role in
1. Initiating cancer
2. Progressing to metastasis
3. Triggering cancer recurrence
4. And developing a resistance to chemo and radiation therapy.
Since current standard treatments miss the mark on cancer stem cells, it is imperative that additional efforts be made to destroy them. Thousands of studies have shown that existing medications can be repurposed to target cancer stem cells. Evidence also shows that dietary supplements and nutrition can also contribute to the fight.
Medical Advice Disclaimer:The information, including but not limited to, text, graphics, images and other material contained on this website are for information purposes only and was based on the latest research accessible to the author at the time of publication. No material on this site is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new healthcare regiment, and never disregard professional medical advice or delay in seeking it because of something you have read on this website.View other articles about the Metabolic Cancer Treatment:
