CHEMOTHERAPY DOES NOT KILL CANCER STEM CELLS THAT PROMOTE METASTASIS.----
This is the Achilles' heel of conventional oncology. It's a critical distinction: reducing the size of a tumor is one thing, but eliminating the root cause that allows it to return is quite another. Cancer stem cells (CSCs) function very differently from other tumor cells, and this is where chemotherapy often fails for three fundamental reasons:
1. The "Quiescent" State
Traditional chemotherapy is designed to attack rapidly dividing cells. However, cancer stem cells can enter a "dormant" state (or cell cycle latency). Since they are not actively dividing at this time, the chemotherapy agent does not recognize them as a target and ignores them.
2. Efflux Pumps
These cells possess a higher number of membrane transporters (such as MDR proteins). When the chemotherapy drug manages to enter the stem cell, the cell detects it and pumps it out before it can damage DNA, becoming virtually immune to the treatment.
3. Resistance to Apoptosis
CSCs have extremely efficient DNA repair mechanisms and very high levels of anti-apoptotic proteins. Even if they are damaged, they have the ability to repair themselves instead of dying.
The Connection to Salicylate and MicroRNAs
Reprogramming vs. Poison: While chemotherapy attempts to "poison" rapidly growing cells, compounds like salicylate attempt to reprogram signaling pathways.
The Role of miR-34: miR-34 has been shown to be a key regulator that can specifically target cancer stem cells, forcing them to differentiate (lose their "mother" status) or sensitizing them so that the immune system or treatments can eliminate them.
Blocking the Wnt pathway: Cancer stem cells rely on signaling pathways such as Wnt/β-catenin to maintain their self-renewal capacity. Salicylate and AMPK activation directly interfere with these pathways.
The danger of "rebound": When chemotherapy kills 99% of common tumor cells but leaves stem cells alive, the remaining tumor becomes much more aggressive. These surviving stem cells now have more space and resources to repopulate the tumor, often with much greater acquired resistance.
For this reason, the modern approach is shifting toward differentiation therapies and the use of metabolic compounds that target AMPK and oxidative stress. The goal is not only to reduce tumor mass but also to "disarm" the stem cells that orchestrate metastasis and recurrence. Salicylate, the active metabolite of aspirin, inhibits the Wnt/β-catenin signaling pathway in colorectal cancer stem cells (CSCs), contributing to the reduction of tumor initiation, progression, and metastasis. This drug specifically targets colorectal cancer stem cells (often characterized as ALDH1+ or DCLK1+ cells) and eliminates them by reducing their ability to form tumor spheres, decreasing the expression of pluripotency genes (e.g., SOX2, OCT4, NANOG, BMI-1, NOTCH1), and inducing apoptosis.
These 2026 studies underscore that success lies not in "killing" the stem cell with toxicity, but in altering its environment by activating AMPK so that it cannot thrive. It's a complete change of strategy: from trying to burn the forest to ensuring that the seeds cannot germinate.
Chemotherapy Doesn't Kill Cancer Stem Cells
This is the Achilles' heel of conventional oncology. It's a critical distinction: reducing the size of a tumor is one thing, but eliminating the root cause that allows it to return is quite another.
Cancer stem cells (CSCs) function very differently from other tumor cells, and this is where chemotherapy often fails for three fundamental reasons:
1. The "Quiescent" State
Traditional chemotherapy is designed to attack rapidly dividing cells. However, cancer stem cells can enter a "dormant" state (or cell cycle latency). Since they are not actively dividing at this time, the chemotherapy agent doesn't recognize them as a target and ignores them.
2. Efflux Pumps
These cells possess a higher number of membrane transporters (such as MDR proteins). When the chemotherapy drug manages to enter the stem cell, the cell detects it and pumps it out before it can damage the DNA, becoming virtually immune to the treatment.
3. Resistance to Apoptosis
CSCs have extremely efficient DNA repair mechanisms and very high levels of anti-apoptotic proteins. Even if they are damaged, they have the ability to repair themselves instead of dying.
The Connection with Salicylate and MicroRNAs
Reprogramming vs. Poison: While chemotherapy attempts to "poison" rapidly growing cells, compounds like salicylate attempt to reprogram signaling pathways.
The Role of miR-34: miR-34 has been shown to be a key regulator that can specifically target cancer stem cells, forcing them to differentiate (lose their "stem" status) or sensitizing them so that the immune system or treatments can eliminate them.
Blocking the Wnt Pathway: Cancer stem cells rely on signaling pathways such as Wnt/β-catenin to maintain their self-renewal capacity. Salicylate and AMPK activation directly interfere with these pathways. The danger of "rebound": When chemotherapy kills 99% of common tumor cells but leaves stem cells alive, the remaining tumor becomes much more aggressive. These surviving stem cells now have more space and resources to repopulate the tumor, often with much greater acquired resistance.
For this reason, the modern approach is shifting toward differentiation therapies and the use of metabolic compounds that act on AMPK and oxidative stress. The goal is not only to reduce tumor mass but also to "disarm" the stem cells that orchestrate metastasis and recurrence.
Salicylate, the active metabolite of aspirin, inhibits the Wnt/β-catenin signaling pathway in colorectal cancer stem cells (CSCs), contributing to the reduction of tumor initiation, progression, and metastasis. This drug specifically targets colorectal cancer stem cells (often characterized as ALDH1+ or DCLK1+ cells) and eliminates them by reducing their ability to form tumor spheres, decreasing the expression of pluripotency genes (e.g., SOX2, OCT4, NANOG, BMI-1, NOTCH1), and inducing apoptosis.
These 2026 studies underscore that success lies not in "killing" the stem cell with toxicity, but in altering its environment by activating AMPK so that it cannot thrive. It's a complete change of strategy: from trying to burn the forest to ensuring that the seeds cannot germinate.
This systematic review synthesizes mechanistic evidence indicating that aspirin exerts anti metastatic effects through coordinated platelet-dependent and tumor-intrinsic pathways, including inhibition of TXA2 signaling, modulation of immune responses, suppression of epithelial–mesenchymal transition, sensitization to anoikis, and miRNA-mediated transcriptional reprogramming. Collectively, these findings provide a coherent biological framework supporting aspirin’s role in limiting metastatic competence. However, given the predominance of preclinical evidence and the limited availability of mechanistically informative clinical studies, definitive conclusions regarding clinical efficacy across cancer types cannot yet be drawn. Nevertheless, the consistency of mechanistic signals across experimental systems supports further investigation of aspirin as a low-cost adjunct in oncology and underscores the need for rigorously designed, biomarker-driven clinical studies to translate these insights into patient benefit.
THE REAL DIFFERENCE BETWEEN NATURAL SALICYLATES IN VEGETABLES AND ACETYLSALICYLIC ACID (ASPIRIN)--The drawback is that it's more difficult to achieve an effective dose.
1. The Chemical "Key": The Acetyl Group
The main difference is that aspirin has an artificially added acetyl group.
• In Aspirin: This acetyl group acts like a "missile" that irreversibly blocks an enzyme called COX-1. This is why aspirin has such a powerful effect in preventing blood clots (antiplatelet), but it's also why it can damage the stomach lining and cause bleeding.
• In Fruits and Vegetables: Natural salicylates do not have this acetyl group. Because they lack it, they don't aggressively attack COX-1. Therefore, they don't usually cause ulcers or bleeding problems, even if you consume vegetables with high levels of salicylates.
• In Fruits and Vegetables: Natural salicylates do not have this acetyl group. Because they lack it, they don't aggressively attack COX-1. Therefore, they don't usually cause ulcers or bleeding problems, even if you consume vegetables with high levels of salicylates. 2. The Final Destination: Salicylic Acid
When you take aspirin, your body quickly cleaves the acetyl group, leaving salicylic acid in your bloodstream—exactly the same thing you get from eating fruits and vegetables.
• The Vegetable Advantage: You get the benefits of salicylic acid (AMPK activation, c-MYC reduction, miR-34 stimulation) without the stomach-irritating acetyl group.
• Dosage and Consistency: A person with a diet rich in vegetables and spices (such as cumin, paprika, or oregano) can maintain blood levels of salicylic acid similar to someone chronically taking infant aspirin, but in a much safer and more natural way.
3. Bioavailability and Synergy
In fruits and vegetables, salicylate doesn't come alone:
• It's accompanied by polyphenols and fiber, which modulate its absorption.
• Consuming broccoli and mustard seeds allows you to activate the natural sulforaphane and salicylates that work together in liver detoxification pathways, something a synthetic pill cannot replicate.
The effect of plant silicates on platelets is very mild/safe. The effect on the stomach is generally protective. It directly activates AMPK. Aspirin is very strong (risk of bleeding) and irritating (risk of ulcers). Its action occurs after metabolism.
In conclusion: The salicylates in fruits and vegetables are the "smart" and safe option. They allow you to activate cancer defense mechanisms (the AMPK pathway mentioned earlier) consistently and daily without worrying about the gastric toxicity or bleeding that pharmaceutical aspirin can cause in the long term.
Spices are the most potent sources of salicylic acid.
Cumin and turmeric: Contain very high levels.
Paprika and cinnamon: Paprika, in particular, has massive concentrations. 1. Oregano, Thyme, and Rosemary: Dried herbs that you can easily add to your smoothies or meals.
Mustard: Activates sulforaphane, also a significant dose of salicylates.
2. Vegetables (Cruciferous and others)
Broccoli and Cauliflower: Excellent sources that also synergize with sulforaphane.
Cucumber and Zucchini: The zucchini you use in your 5 pm smoothie is a consistent source.
Peppers (especially hot or very red ones): Contain high levels.
Radishes: Ideal to combine with cruciferous vegetables.
3. Fruits (Berries and Forest Fruits)
Fruits with intense colors tend to have a higher content:
Raspberries and Strawberries: They are the queens of salicylic acid in the fruit kingdom.
Blueberries and Blackberries: Highly recommended for their additional antioxidant content. Dates and Raisins: They have a very high concentration, although they should be consumed in moderation due to their glucose level.
Great report. It's fascinating how science is rediscovering ancient compounds through the lens of modern molecular biology. The mechanism you describe is indeed astonishingly elegant because it doesn't rely on an external cytotoxic attack, but rather on restoring the cell's metabolic intelligence.
It's a paradigm shift: moving from simply inhibiting inflammation (via COX) to epigenetic and metabolic modulation.
Three steps you mention are so disruptive in preventive oncology:
1. Salicylate as a Metabolic "Trojan Horse"
By activating AMPK, salicylate tricks the cancer cell into believing there's an energy crisis.
• The cancer trap: Tumor cells are addicted to consuming energy for their uncontrolled division.
• The effect: When the fuel sensor (AMPK) is activated, the cell is forced to halt cell building processes (anabolism) and prioritize survival, which abruptly stops the cell division cycle that the c-MYC gene tries to maintain at all costs.
2. The release of NRF2 and the p53 bypass
This is the most revolutionary aspect of the research you cite.
• The p53 problem: Historically, it was thought that if the p53 gene (the "guardian") was mutated or absent, the cell was doomed to become cancerous because it could not activate suppressor microRNAs like miR-34.
• The salicylate solution: By removing c-MYC's block on NRF2, salicylate opens a "back door." NRF2 takes over and activates the defenses (miR-34) without needing p53. This is like having a secondary fire suppression system that activates when the main panel fails.
3. Salicylate vs. Aspirin: The Importance of the Acetyl Group
This article touches on a crucial point: the difference between aspirin (acetylsalicylic acid) and salicylate (salicylic acid).
• Aspirin rapidly breaks down into salicylate in the body.
• The main antitumor effect comes from salicylate and its interaction with AMPK. This opens the door to using forms of salicylates that could be less aggressive to the gastric mucosa than conventional aspirin, since we would not depend exclusively on COX-1 inhibition to obtain the preventive benefit.
This mechanism reinforces the idea that fighting cancer is not just about "killing" cells, but about reprogramming the cellular environment so that the body itself regains control of its growth.
This is a very powerful perspective, especially considering that c-MYC is a target that the pharmaceutical industry has unsuccessfully tried to block with complex drugs for decades, and it turns out that a compound derived from willow bark might hold the key.
“ASCOLT 2025 Protocol”: This is the definitive study on aspirin after colon surgery.
The ASCOLT (Aspirin after completion of standard adjuvant therapy for colorectal cancer) trial is a major international, randomized, double-blind, phase 3 study exploring whether aspirin can improve survival outcomes in patients with resected stage II and III colorectal cancer. Results published in early 2025 indicated that while aspirin was well-tolerated, daily administration did not significantly improve disease-free survival.
“AMPK-MYC Salicylate Axis”: The elegant mechanism you yourself described.
Salicylate (the active metabolite of aspirin) exerts a potent chemopreventive and antitumor effect in colorectal cancer through the regulation of the AMPK-MYC axis. This mechanism acts as a metabolic switch that induces the degradation of the c-MYC oncogene.
“ALASSCA Study”: The one that links aspirin to the PIK3CA gene.
“ALASSCA Study” The ALASCCA (Adjuvant Low Dose Aspirin in Colorectal Cancer) study is a randomized, double-blind clinical trial investigating whether low-dose aspirin (160 mg daily) can reduce the risk of recurrence in patients with colorectal cancer, specifically those with a PIK3CA gene mutation. This adjuvant treatment aims to improve survival by inhibiting tumor-specific metabolic pathways.
Fight, fight, fight! War on Cancer...War on - fill in the blank. Poison for medicines, Militaristic approach, kill the Dis - Ease and maybe we don't kill you. If we do...whoopsie. How revolutionary...science to heal, science to prevent Dis-Ease, science to create, build and maintain actual Real Health. How welcome to see an approach to return, to heal the body to be able to perform in a healthy range. With so many toxic offenders of so many sorts and kinds this is welcomed hope for those who focus on the practice of health building but some can still get bit by Dis-Ease. The focus on supporting our foundation, ( the Mitochondria,) feeding all the other functions and systems of our bodies there may be other remedy's similar to this for cancers. Bring back the harmony and balance for health the body pursues if allowed.
Recent reports show Ivermectin on its own, another compound and then the two combined seem to remove cancer. Just wondering if these use a similar affect as the aspirin?
Yes, Just, IVERMECTIN HAS AT LEAST 15 ANTI-CANCER MECHANISMS OF ACTION. CAN IT TREAT COVID-19 MRNA VACCINE-INDUCED TURBO CANCERS?IVERMECTIN INDUCES TUMOR CELL DEATH: APOPTOSIS, AUTOPHAGY, PYROPTOSIS
3) Ivermectin stops cancer cell migration, invasion and metastasis (via PAK1 inhibition – seen in 70% of all cancers, EMT inhibition, RNA Helicase inhibition)
4) Ivermectin causes cancer cell mitochondrial dysfunction (inhibits mitochondrial biogenesis, increases reactive oxygen species selectively only in cancer cells)
5) Ivermectin regulates tumor microenvironment (to inhibit tumor growth and progression, via P2X7 path, ICD – mediates immunogenic cell death)
6) Ivermectin inhibits cancer stem cells (which are responsible for tumor initiation, progression and recurrence)
8) Ivermectin has anti-mitotic activity (interacts with mammalian tubulin)
9) Ivermectin is an epigenetic regulator of cancer to inhibit cancer progression(alters gene expression to inhibit cancer progression, SIN3A, EMT)
10) Ivermectin can overcome tumor multidrug resistance
The top 5 COVID-19 mRNA Vaccine Induced Turbo Cancers are: lymphomas, brain
cancers, breast cancers, colon cancers and lung cancers (signals also seen in leukemias, hepatobiliary cancers, testicular cancers, sarcomas and melanomas)
Ivermectin has been shown to kill these cancer cells (in vitro or in vivo):
Many studies have shown that ivermectin exerts antitumor effects and, therefore, could benefit cancer patients after sufficient clinical trials. It is also an inducer of mitochondrial dysfunction and oxidative stress. Ivermectin has this potential because it modulates several targets, including the multidrug resistance protein, the Akt/mTOR and WNT-TCF pathways, purinergic receptors, the PAK-1 protein, and certain cancer-related epigenetic dysregulators such as SIN3A and SIN3B. It activates RNA helicase, while also stimulating chloride channel receptors, leading to cellular hyperpolarization and downregulating stem cell genes to preferentially target the cancer stem cell population, at least in breast cancer.
The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug
Progress in understanding the molecular mechanisms and understanding the antitumor effects of ivermectin.
Many studies have shown that ivermectin exerts antitumor effects and therefore could benefit cancer patients after sufficient clinical trials. It is also an inducer of mitochondrial dysfunction and oxidative stress. Ivermectin has this potential as it modulates various targets such as the multidrug resistance protein, the Akt/mTOR and WNT-TCF pathways, purinergic receptors, the PAK-1 protein, certain cancer-related epigenetic dysregulators such as SIN3A and SIN3B, activate RNA helicase, while stimulating chloride channel receptors that lead to cell hyperpolarization and down-regulate maternal genes to preferentially target the cancer stem cell population, at least in breast cancer.
ANTI-PARASITE DRUG IVERMECTIN CAN SUPPRESS OVARIAN CANCER BY REGULATING LNCRNA-EIF4A3-MRNA AXES.
Those findings provided the potential targeted lncRNA-EIF4A3-mRNA pathways of ivermectin in OCs, and constructed the effective prognostic model, which benefits discovery of novel mechanism of ivermectin to suppress ovarian cancer cells, and the ivermectin-related molecule-panel changes benefit for its personalized drug therapy and prognostic assessment towards its predictive, preventive, and personalized medicine (PPPM) in OCs.
IVERMECTIN CONVERTS COLD TUMORS HOT AND SYNERGIZES WITH IMMUNE CHECKPOINT BLOCKADE FOR TREATMENT OF BREAST CANCER.
Ivermectin induces immunogenic cancer cell death (ICD) and strong T cell infiltration into breast tumors. As an allosteric modulator of the ATP/P2X4/P2X7 axis operating in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations, including myeloid cells and Tregs, resulting in an enhanced Teff/Tregs ratio. This effectively converts "cold" tumors into "hot" tumors, making it a rational mechanistic partner for checkpoint blockade.
IVERMECTIN: POTENTIAL REPURPOSING OF A VERSATILE ANTIPARASITIC AS A NOVEL ANTICANCER.
Ivermectin has demonstrated antitumor effects in various types of cancer. Among the reported mechanisms of action, ivermectin interacts with and affects the function of mitochondrial complex I, the multidrug resistance (MDR) protein, RNA helicases, the WNT-TCF pathway, the chloride channel receptor, immunogenic cell death via ATP- and HMGB1, PAK-1, epigenetic signature, and stem cell self-renewal. Preclinical tests have demonstrated cell growth inhibition, apoptosis induction in various cancer cell lines, and antitumor effects. Antitumor effects are observed at a mean concentration of 5 μM (0.01–100 μM), which is clinically achievable according to the human pharmacokinetic data shown in Table 1. A review of laboratory results for ivermectin in several cancer cell lines is presented.
IVERMECTIN CONVERTS COLD TUMORS HOT AND SYNERGIZES WITH IMMUNE CHECKPOINT BLOCKADE FOR TREATMENT OF BREAST CANCER.
Ivermectin induces the death of immunogenic cancer cells (ICD) and a strong infiltration of T cells in breast tumors. As an allosteric modulator of the ATP / P2X4 / P2X7 axis operating in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations, including myeloid cells and Tregs, resulting in an improved Teff / Tregs ratio. turning cold tumors into hot ones, thus representing a rational mechanistic partner with checkpoint blocking.
IVERMECTIN: POTENTIAL REPURPOSING OF A VERSATILE ANTIPARASITIC AS A NOVEL ANTICANCER.
Ivermectin has shown antitumor effects in different types of cancers. Among the reported mechanisms of action, ivermectin interacts with and affects the function of mitochondrial complex I, multidrug resistance protein (MDR), RNA helicases, the WNT-TCF pathway, the chloride channel receptor, the cell immunogenic death through ATP- and HMGB1, PAK-1, epigenetic signature and stem cell self-renewal. Preclinical tests have shown inhibition of cell growth, induction of apoptosis in different cancer cell lines, and antitumor effects. Antitumor effects are observed at a mean concentration of 5 μM (0.01-100 μM), which is clinically achievable based on the human pharmacokinetic data shown in Table 1. A review of laboratory results for ivermectin in various cancer cell lines is presented.
Your comment is spot on, Just. I'll reply here and on the website. With war, the landowners' estates increase, the misery of the poor increases, the general's speeches increase, and the silence of men grows. Bertolt Brecht.--------------
In any armed conflict, there are two fronts: the battlefront, with bombs, drones, and shrapnel; and the rearguard, which operates silently and devastatingly. In this second arena, hunger, thirst, darkness, and demoralization are used as weapons to destroy a people's resistance.
In Gaza, and now in Iran, this strategy is tragically evident. The Israeli army has not only attacked civilian infrastructure such as hospitals, schools, and homes, but has also deliberately blocked the entry of food, water, and energy. Some one hundred thousand Palestinian children are now at serious risk of malnutrition. It is genocide by starvation. To die of hunger or to die from a gunshot wound: this is the infernal dilemma faced by the trapped population.
Hunger is a weapon of slow but relentless destruction. Acute malnutrition appears suddenly, often associated with emergency situations such as wars, natural disasters, or economic blockades. It causes rapid weight loss, extreme weakness, digestive problems, and a high risk of infections due to a weakened immune system. In children, chronic hunger leads to irreversible impairments in physical and cognitive development. In adults, it can cause heart, respiratory, and immune problems, with the ultimate risk of death.
In recent history, we know of extreme cases of resistance to hunger: the mayor of Cork, Ireland, on a hunger strike for political reasons, survived seventy-four days on water alone. But most victims of hunger do not choose their fate: they are civilians trapped by inhumane strategies.
Hunger is not just a medical problem: it is an ethical and geopolitical issue. Using it as a weapon is a flagrant violation of international humanitarian law. It is a slow form of extermination, a war crime, and the international community cannot turn a blind eye. There can be no peace without food justice. There can be no humanity while a single child dies of hunger as a deliberate consequence of conflict. In the face of this tragedy, silence is not neutrality: it is complicity.
Wars shrink the pie for the 99%, yet increase the portions of pie for the 1%. While parts of the world are suffering the bombs, the bullets, as well as hunger, thirst, darkness and despair, the "civilized Country's are in tandem are facing increasing Hunger for clean, healthy foods, thirst for uncontaminated water, facing calls of coming energy shortages and the darkness of despair all these things bring. Revolutionary - the Pursuit of ways to Heal and Not Steal increasing a pie for all.
CHEMOTHERAPY DOES NOT KILL CANCER STEM CELLS THAT PROMOTE METASTASIS.----
This is the Achilles' heel of conventional oncology. It's a critical distinction: reducing the size of a tumor is one thing, but eliminating the root cause that allows it to return is quite another. Cancer stem cells (CSCs) function very differently from other tumor cells, and this is where chemotherapy often fails for three fundamental reasons:
1. The "Quiescent" State
Traditional chemotherapy is designed to attack rapidly dividing cells. However, cancer stem cells can enter a "dormant" state (or cell cycle latency). Since they are not actively dividing at this time, the chemotherapy agent does not recognize them as a target and ignores them.
2. Efflux Pumps
These cells possess a higher number of membrane transporters (such as MDR proteins). When the chemotherapy drug manages to enter the stem cell, the cell detects it and pumps it out before it can damage DNA, becoming virtually immune to the treatment.
3. Resistance to Apoptosis
CSCs have extremely efficient DNA repair mechanisms and very high levels of anti-apoptotic proteins. Even if they are damaged, they have the ability to repair themselves instead of dying.
The Connection to Salicylate and MicroRNAs
Reprogramming vs. Poison: While chemotherapy attempts to "poison" rapidly growing cells, compounds like salicylate attempt to reprogram signaling pathways.
The Role of miR-34: miR-34 has been shown to be a key regulator that can specifically target cancer stem cells, forcing them to differentiate (lose their "mother" status) or sensitizing them so that the immune system or treatments can eliminate them.
Blocking the Wnt pathway: Cancer stem cells rely on signaling pathways such as Wnt/β-catenin to maintain their self-renewal capacity. Salicylate and AMPK activation directly interfere with these pathways.
The danger of "rebound": When chemotherapy kills 99% of common tumor cells but leaves stem cells alive, the remaining tumor becomes much more aggressive. These surviving stem cells now have more space and resources to repopulate the tumor, often with much greater acquired resistance.
For this reason, the modern approach is shifting toward differentiation therapies and the use of metabolic compounds that target AMPK and oxidative stress. The goal is not only to reduce tumor mass but also to "disarm" the stem cells that orchestrate metastasis and recurrence. Salicylate, the active metabolite of aspirin, inhibits the Wnt/β-catenin signaling pathway in colorectal cancer stem cells (CSCs), contributing to the reduction of tumor initiation, progression, and metastasis. This drug specifically targets colorectal cancer stem cells (often characterized as ALDH1+ or DCLK1+ cells) and eliminates them by reducing their ability to form tumor spheres, decreasing the expression of pluripotency genes (e.g., SOX2, OCT4, NANOG, BMI-1, NOTCH1), and inducing apoptosis.
These 2026 studies underscore that success lies not in "killing" the stem cell with toxicity, but in altering its environment by activating AMPK so that it cannot thrive. It's a complete change of strategy: from trying to burn the forest to ensuring that the seeds cannot germinate.
Chemotherapy Doesn't Kill Cancer Stem Cells
This is the Achilles' heel of conventional oncology. It's a critical distinction: reducing the size of a tumor is one thing, but eliminating the root cause that allows it to return is quite another.
Cancer stem cells (CSCs) function very differently from other tumor cells, and this is where chemotherapy often fails for three fundamental reasons:
1. The "Quiescent" State
Traditional chemotherapy is designed to attack rapidly dividing cells. However, cancer stem cells can enter a "dormant" state (or cell cycle latency). Since they are not actively dividing at this time, the chemotherapy agent doesn't recognize them as a target and ignores them.
2. Efflux Pumps
These cells possess a higher number of membrane transporters (such as MDR proteins). When the chemotherapy drug manages to enter the stem cell, the cell detects it and pumps it out before it can damage the DNA, becoming virtually immune to the treatment.
3. Resistance to Apoptosis
CSCs have extremely efficient DNA repair mechanisms and very high levels of anti-apoptotic proteins. Even if they are damaged, they have the ability to repair themselves instead of dying.
The Connection with Salicylate and MicroRNAs
Reprogramming vs. Poison: While chemotherapy attempts to "poison" rapidly growing cells, compounds like salicylate attempt to reprogram signaling pathways.
The Role of miR-34: miR-34 has been shown to be a key regulator that can specifically target cancer stem cells, forcing them to differentiate (lose their "stem" status) or sensitizing them so that the immune system or treatments can eliminate them.
Blocking the Wnt Pathway: Cancer stem cells rely on signaling pathways such as Wnt/β-catenin to maintain their self-renewal capacity. Salicylate and AMPK activation directly interfere with these pathways. The danger of "rebound": When chemotherapy kills 99% of common tumor cells but leaves stem cells alive, the remaining tumor becomes much more aggressive. These surviving stem cells now have more space and resources to repopulate the tumor, often with much greater acquired resistance.
For this reason, the modern approach is shifting toward differentiation therapies and the use of metabolic compounds that act on AMPK and oxidative stress. The goal is not only to reduce tumor mass but also to "disarm" the stem cells that orchestrate metastasis and recurrence.
Salicylate, the active metabolite of aspirin, inhibits the Wnt/β-catenin signaling pathway in colorectal cancer stem cells (CSCs), contributing to the reduction of tumor initiation, progression, and metastasis. This drug specifically targets colorectal cancer stem cells (often characterized as ALDH1+ or DCLK1+ cells) and eliminates them by reducing their ability to form tumor spheres, decreasing the expression of pluripotency genes (e.g., SOX2, OCT4, NANOG, BMI-1, NOTCH1), and inducing apoptosis.
These 2026 studies underscore that success lies not in "killing" the stem cell with toxicity, but in altering its environment by activating AMPK so that it cannot thrive. It's a complete change of strategy: from trying to burn the forest to ensuring that the seeds cannot germinate.
https://pmc.ncbi.nlm.nih.gov/articles/PMC8941648/ (2022)
https://pmc.ncbi.nlm.nih.gov/articles/PMC7348976/ (2020)
https://pmc.ncbi.nlm.nih.gov/articles/PMC7797380/ (2020)
https://www.nature.com/articles/s41419-026-08707-z (2026)
https://www.mdpi.com/1422-0067/25/16/8647 (2024)
https://www.mdpi.com/1422-0067/25/20/11185 (2025)
https://www.spandidos-publications.com/10.3892/wasj.2025.391 (2025)
https://pmc.ncbi.nlm.nih.gov/articles/PMC11856717/ (2025)
This systematic review synthesizes mechanistic evidence indicating that aspirin exerts anti metastatic effects through coordinated platelet-dependent and tumor-intrinsic pathways, including inhibition of TXA2 signaling, modulation of immune responses, suppression of epithelial–mesenchymal transition, sensitization to anoikis, and miRNA-mediated transcriptional reprogramming. Collectively, these findings provide a coherent biological framework supporting aspirin’s role in limiting metastatic competence. However, given the predominance of preclinical evidence and the limited availability of mechanistically informative clinical studies, definitive conclusions regarding clinical efficacy across cancer types cannot yet be drawn. Nevertheless, the consistency of mechanistic signals across experimental systems supports further investigation of aspirin as a low-cost adjunct in oncology and underscores the need for rigorously designed, biomarker-driven clinical studies to translate these insights into patient benefit.
https://www.mdpi.com/1422-0067/27/3/1288 (2026)
THE REAL DIFFERENCE BETWEEN NATURAL SALICYLATES IN VEGETABLES AND ACETYLSALICYLIC ACID (ASPIRIN)--The drawback is that it's more difficult to achieve an effective dose.
1. The Chemical "Key": The Acetyl Group
The main difference is that aspirin has an artificially added acetyl group.
• In Aspirin: This acetyl group acts like a "missile" that irreversibly blocks an enzyme called COX-1. This is why aspirin has such a powerful effect in preventing blood clots (antiplatelet), but it's also why it can damage the stomach lining and cause bleeding.
• In Fruits and Vegetables: Natural salicylates do not have this acetyl group. Because they lack it, they don't aggressively attack COX-1. Therefore, they don't usually cause ulcers or bleeding problems, even if you consume vegetables with high levels of salicylates.
• In Fruits and Vegetables: Natural salicylates do not have this acetyl group. Because they lack it, they don't aggressively attack COX-1. Therefore, they don't usually cause ulcers or bleeding problems, even if you consume vegetables with high levels of salicylates. 2. The Final Destination: Salicylic Acid
When you take aspirin, your body quickly cleaves the acetyl group, leaving salicylic acid in your bloodstream—exactly the same thing you get from eating fruits and vegetables.
• The Vegetable Advantage: You get the benefits of salicylic acid (AMPK activation, c-MYC reduction, miR-34 stimulation) without the stomach-irritating acetyl group.
• Dosage and Consistency: A person with a diet rich in vegetables and spices (such as cumin, paprika, or oregano) can maintain blood levels of salicylic acid similar to someone chronically taking infant aspirin, but in a much safer and more natural way.
3. Bioavailability and Synergy
In fruits and vegetables, salicylate doesn't come alone:
• It's accompanied by polyphenols and fiber, which modulate its absorption.
• Consuming broccoli and mustard seeds allows you to activate the natural sulforaphane and salicylates that work together in liver detoxification pathways, something a synthetic pill cannot replicate.
The effect of plant silicates on platelets is very mild/safe. The effect on the stomach is generally protective. It directly activates AMPK. Aspirin is very strong (risk of bleeding) and irritating (risk of ulcers). Its action occurs after metabolism.
In conclusion: The salicylates in fruits and vegetables are the "smart" and safe option. They allow you to activate cancer defense mechanisms (the AMPK pathway mentioned earlier) consistently and daily without worrying about the gastric toxicity or bleeding that pharmaceutical aspirin can cause in the long term.
Spices are the most potent sources of salicylic acid.
Cumin and turmeric: Contain very high levels.
Paprika and cinnamon: Paprika, in particular, has massive concentrations. 1. Oregano, Thyme, and Rosemary: Dried herbs that you can easily add to your smoothies or meals.
Mustard: Activates sulforaphane, also a significant dose of salicylates.
2. Vegetables (Cruciferous and others)
Broccoli and Cauliflower: Excellent sources that also synergize with sulforaphane.
Cucumber and Zucchini: The zucchini you use in your 5 pm smoothie is a consistent source.
Peppers (especially hot or very red ones): Contain high levels.
Radishes: Ideal to combine with cruciferous vegetables.
3. Fruits (Berries and Forest Fruits)
Fruits with intense colors tend to have a higher content:
Raspberries and Strawberries: They are the queens of salicylic acid in the fruit kingdom.
Blueberries and Blackberries: Highly recommended for their additional antioxidant content. Dates and Raisins: They have a very high concentration, although they should be consumed in moderation due to their glucose level.
Great report. It's fascinating how science is rediscovering ancient compounds through the lens of modern molecular biology. The mechanism you describe is indeed astonishingly elegant because it doesn't rely on an external cytotoxic attack, but rather on restoring the cell's metabolic intelligence.
It's a paradigm shift: moving from simply inhibiting inflammation (via COX) to epigenetic and metabolic modulation.
Three steps you mention are so disruptive in preventive oncology:
1. Salicylate as a Metabolic "Trojan Horse"
By activating AMPK, salicylate tricks the cancer cell into believing there's an energy crisis.
• The cancer trap: Tumor cells are addicted to consuming energy for their uncontrolled division.
• The effect: When the fuel sensor (AMPK) is activated, the cell is forced to halt cell building processes (anabolism) and prioritize survival, which abruptly stops the cell division cycle that the c-MYC gene tries to maintain at all costs.
2. The release of NRF2 and the p53 bypass
This is the most revolutionary aspect of the research you cite.
• The p53 problem: Historically, it was thought that if the p53 gene (the "guardian") was mutated or absent, the cell was doomed to become cancerous because it could not activate suppressor microRNAs like miR-34.
• The salicylate solution: By removing c-MYC's block on NRF2, salicylate opens a "back door." NRF2 takes over and activates the defenses (miR-34) without needing p53. This is like having a secondary fire suppression system that activates when the main panel fails.
3. Salicylate vs. Aspirin: The Importance of the Acetyl Group
This article touches on a crucial point: the difference between aspirin (acetylsalicylic acid) and salicylate (salicylic acid).
• Aspirin rapidly breaks down into salicylate in the body.
• The main antitumor effect comes from salicylate and its interaction with AMPK. This opens the door to using forms of salicylates that could be less aggressive to the gastric mucosa than conventional aspirin, since we would not depend exclusively on COX-1 inhibition to obtain the preventive benefit.
• Pathway Summary:
Salicylate→↑AMPK→↓c−MYC→↑NRF2→↑miR−34→Tumor Suppression
This mechanism reinforces the idea that fighting cancer is not just about "killing" cells, but about reprogramming the cellular environment so that the body itself regains control of its growth.
This is a very powerful perspective, especially considering that c-MYC is a target that the pharmaceutical industry has unsuccessfully tried to block with complex drugs for decades, and it turns out that a compound derived from willow bark might hold the key.
“ASCOLT 2025 Protocol”: This is the definitive study on aspirin after colon surgery.
The ASCOLT (Aspirin after completion of standard adjuvant therapy for colorectal cancer) trial is a major international, randomized, double-blind, phase 3 study exploring whether aspirin can improve survival outcomes in patients with resected stage II and III colorectal cancer. Results published in early 2025 indicated that while aspirin was well-tolerated, daily administration did not significantly improve disease-free survival.
“AMPK-MYC Salicylate Axis”: The elegant mechanism you yourself described.
Salicylate (the active metabolite of aspirin) exerts a potent chemopreventive and antitumor effect in colorectal cancer through the regulation of the AMPK-MYC axis. This mechanism acts as a metabolic switch that induces the degradation of the c-MYC oncogene.
“ALASSCA Study”: The one that links aspirin to the PIK3CA gene.
“ALASSCA Study” The ALASCCA (Adjuvant Low Dose Aspirin in Colorectal Cancer) study is a randomized, double-blind clinical trial investigating whether low-dose aspirin (160 mg daily) can reduce the risk of recurrence in patients with colorectal cancer, specifically those with a PIK3CA gene mutation. This adjuvant treatment aims to improve survival by inhibiting tumor-specific metabolic pathways.
https://www.cam.ac.uk/research/news/scientists-discover-how-aspirin-could-prevent-some-cancers-from-spreading (2025)
https://www.mdpi.com/1422-0067/27/3/1288 (2025)
https://www.mdpi.com/2076-3921/14/1/29 (2024)
https://www.nature.com/articles/s41419-023-06226-9 (2023)
https://portal.findresearcher.sdu.dk/en/publications/salicylate-elicited-activation-of-amp-activated-protein-kinase-di/ (2025)
https://www.sciencedirect.com/science/article/abs/pii/S0002961026002114 (2026)
https://www.thelancet.com/journals/langas/article/PIIS2468-1253(2400387-X/abstract (2026)
https://www.bjsacademy.com/bjs-academy/randomized-clinical-trials/aspirin-after-completion-of-standard-adjuvant-therapy-for-colorectal-cancer-ascolt-an-international-multicentre-phase-3-randomised-double-blind-placebo-controlled-trial (2026)
https://www.nccs.com.sg/news/research/conclusion-of-global-multicentre-trial-defines-aspirins-role-in-reducing-colorectal-cancer-recurrence (2025)
https://pubmed.ncbi.nlm.nih.gov/39824200/ (2025)
https://clinicaltrials.gov/study/NCT02647099 (2026)
Fight, fight, fight! War on Cancer...War on - fill in the blank. Poison for medicines, Militaristic approach, kill the Dis - Ease and maybe we don't kill you. If we do...whoopsie. How revolutionary...science to heal, science to prevent Dis-Ease, science to create, build and maintain actual Real Health. How welcome to see an approach to return, to heal the body to be able to perform in a healthy range. With so many toxic offenders of so many sorts and kinds this is welcomed hope for those who focus on the practice of health building but some can still get bit by Dis-Ease. The focus on supporting our foundation, ( the Mitochondria,) feeding all the other functions and systems of our bodies there may be other remedy's similar to this for cancers. Bring back the harmony and balance for health the body pursues if allowed.
Recent reports show Ivermectin on its own, another compound and then the two combined seem to remove cancer. Just wondering if these use a similar affect as the aspirin?
Yes, Just, IVERMECTIN HAS AT LEAST 15 ANTI-CANCER MECHANISMS OF ACTION. CAN IT TREAT COVID-19 MRNA VACCINE-INDUCED TURBO CANCERS?IVERMECTIN INDUCES TUMOR CELL DEATH: APOPTOSIS, AUTOPHAGY, PYROPTOSIS
https://www.sciencedirect.com/science/article/pii/S1043661820315152
Summarize the anti-cancer mechanisms
https://jlar.rovedar.com/index.php/JLAR/article/view/11/21
1) Ivermectin inhibits tumor initiation and tumor progression (via WNT inhibition, YAP1 inhibition)
2) Ivermectin inhibits tumor growth and proliferation (via Akt/mTOR inhibition, MAPK inhibition)
3) Ivermectin stops cancer cell migration, invasion and metastasis (via PAK1 inhibition – seen in 70% of all cancers, EMT inhibition, RNA Helicase inhibition)
4) Ivermectin causes cancer cell mitochondrial dysfunction (inhibits mitochondrial biogenesis, increases reactive oxygen species selectively only in cancer cells)
5) Ivermectin regulates tumor microenvironment (to inhibit tumor growth and progression, via P2X7 path, ICD – mediates immunogenic cell death)
6) Ivermectin inhibits cancer stem cells (which are responsible for tumor initiation, progression and recurrence)
7) Ivermectin inhibits tumor angiogenesis (tumor blood vessel creation)
8) Ivermectin has anti-mitotic activity (interacts with mammalian tubulin)
9) Ivermectin is an epigenetic regulator of cancer to inhibit cancer progression(alters gene expression to inhibit cancer progression, SIN3A, EMT)
10) Ivermectin can overcome tumor multidrug resistance
The top 5 COVID-19 mRNA Vaccine Induced Turbo Cancers are: lymphomas, brain
cancers, breast cancers, colon cancers and lung cancers (signals also seen in leukemias, hepatobiliary cancers, testicular cancers, sarcomas and melanomas)
Ivermectin has been shown to kill these cancer cells (in vitro or in vivo):
https://www.globalresearch.ca/ivermectin-15-anti-cancer-mechanisms-action-treat-covid-19-mrna-vaccine-induced-turbo-cancers/5834622 (10/02/2023)
Many studies have shown that ivermectin exerts antitumor effects and, therefore, could benefit cancer patients after sufficient clinical trials. It is also an inducer of mitochondrial dysfunction and oxidative stress. Ivermectin has this potential because it modulates several targets, including the multidrug resistance protein, the Akt/mTOR and WNT-TCF pathways, purinergic receptors, the PAK-1 protein, and certain cancer-related epigenetic dysregulators such as SIN3A and SIN3B. It activates RNA helicase, while also stimulating chloride channel receptors, leading to cellular hyperpolarization and downregulating stem cell genes to preferentially target the cancer stem cell population, at least in breast cancer.
The multitargeted drug ivermectin: from an antiparasitic agent to a repositioned cancer drug
Progress in understanding the molecular mechanisms and understanding the antitumor effects of ivermectin.
Many studies have shown that ivermectin exerts antitumor effects and therefore could benefit cancer patients after sufficient clinical trials. It is also an inducer of mitochondrial dysfunction and oxidative stress. Ivermectin has this potential as it modulates various targets such as the multidrug resistance protein, the Akt/mTOR and WNT-TCF pathways, purinergic receptors, the PAK-1 protein, certain cancer-related epigenetic dysregulators such as SIN3A and SIN3B, activate RNA helicase, while stimulating chloride channel receptors that lead to cell hyperpolarization and down-regulate maternal genes to preferentially target the cancer stem cell population, at least in breast cancer.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5835698/ (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982461/ (2020)
ANTI-PARASITE DRUG IVERMECTIN CAN SUPPRESS OVARIAN CANCER BY REGULATING LNCRNA-EIF4A3-MRNA AXES.
Those findings provided the potential targeted lncRNA-EIF4A3-mRNA pathways of ivermectin in OCs, and constructed the effective prognostic model, which benefits discovery of novel mechanism of ivermectin to suppress ovarian cancer cells, and the ivermectin-related molecule-panel changes benefit for its personalized drug therapy and prognostic assessment towards its predictive, preventive, and personalized medicine (PPPM) in OCs.
https://link.springer.com/content/pdf/10.1007/s13167-020-00209-y.pdf (2020)
IVERMECTIN CONVERTS COLD TUMORS HOT AND SYNERGIZES WITH IMMUNE CHECKPOINT BLOCKADE FOR TREATMENT OF BREAST CANCER.
Ivermectin induces immunogenic cancer cell death (ICD) and strong T cell infiltration into breast tumors. As an allosteric modulator of the ATP/P2X4/P2X7 axis operating in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations, including myeloid cells and Tregs, resulting in an enhanced Teff/Tregs ratio. This effectively converts "cold" tumors into "hot" tumors, making it a rational mechanistic partner for checkpoint blockade.
https://www.nature.com/articles/s41523-021-00229-5 (2021)
IVERMECTIN: POTENTIAL REPURPOSING OF A VERSATILE ANTIPARASITIC AS A NOVEL ANTICANCER.
Ivermectin has demonstrated antitumor effects in various types of cancer. Among the reported mechanisms of action, ivermectin interacts with and affects the function of mitochondrial complex I, the multidrug resistance (MDR) protein, RNA helicases, the WNT-TCF pathway, the chloride channel receptor, immunogenic cell death via ATP- and HMGB1, PAK-1, epigenetic signature, and stem cell self-renewal. Preclinical tests have demonstrated cell growth inhibition, apoptosis induction in various cancer cell lines, and antitumor effects. Antitumor effects are observed at a mean concentration of 5 μM (0.01–100 μM), which is clinically achievable according to the human pharmacokinetic data shown in Table 1. A review of laboratory results for ivermectin in several cancer cell lines is presented.
https://www.intechopen.com/online-first/78376 (2021)
IVERMECTIN CONVERTS COLD TUMORS HOT AND SYNERGIZES WITH IMMUNE CHECKPOINT BLOCKADE FOR TREATMENT OF BREAST CANCER.
Ivermectin induces the death of immunogenic cancer cells (ICD) and a strong infiltration of T cells in breast tumors. As an allosteric modulator of the ATP / P2X4 / P2X7 axis operating in both cancer and immune cells, ivermectin also selectively targets immunosuppressive populations, including myeloid cells and Tregs, resulting in an improved Teff / Tregs ratio. turning cold tumors into hot ones, thus representing a rational mechanistic partner with checkpoint blocking.
https://www.nature.com/articles/s41523-021-00229-5 (2021)
IVERMECTIN: POTENTIAL REPURPOSING OF A VERSATILE ANTIPARASITIC AS A NOVEL ANTICANCER.
Ivermectin has shown antitumor effects in different types of cancers. Among the reported mechanisms of action, ivermectin interacts with and affects the function of mitochondrial complex I, multidrug resistance protein (MDR), RNA helicases, the WNT-TCF pathway, the chloride channel receptor, the cell immunogenic death through ATP- and HMGB1, PAK-1, epigenetic signature and stem cell self-renewal. Preclinical tests have shown inhibition of cell growth, induction of apoptosis in different cancer cell lines, and antitumor effects. Antitumor effects are observed at a mean concentration of 5 μM (0.01-100 μM), which is clinically achievable based on the human pharmacokinetic data shown in Table 1. A review of laboratory results for ivermectin in various cancer cell lines is presented.
https://www.intechopen.com/online-first/78376 (2021)
No wonder Ivermectin was suppressed, unexpected consequences it works outside of needing lifetime treadmill treatments.
Your comment is spot on, Just. I'll reply here and on the website. With war, the landowners' estates increase, the misery of the poor increases, the general's speeches increase, and the silence of men grows. Bertolt Brecht.--------------
In any armed conflict, there are two fronts: the battlefront, with bombs, drones, and shrapnel; and the rearguard, which operates silently and devastatingly. In this second arena, hunger, thirst, darkness, and demoralization are used as weapons to destroy a people's resistance.
In Gaza, and now in Iran, this strategy is tragically evident. The Israeli army has not only attacked civilian infrastructure such as hospitals, schools, and homes, but has also deliberately blocked the entry of food, water, and energy. Some one hundred thousand Palestinian children are now at serious risk of malnutrition. It is genocide by starvation. To die of hunger or to die from a gunshot wound: this is the infernal dilemma faced by the trapped population.
Hunger is a weapon of slow but relentless destruction. Acute malnutrition appears suddenly, often associated with emergency situations such as wars, natural disasters, or economic blockades. It causes rapid weight loss, extreme weakness, digestive problems, and a high risk of infections due to a weakened immune system. In children, chronic hunger leads to irreversible impairments in physical and cognitive development. In adults, it can cause heart, respiratory, and immune problems, with the ultimate risk of death.
In recent history, we know of extreme cases of resistance to hunger: the mayor of Cork, Ireland, on a hunger strike for political reasons, survived seventy-four days on water alone. But most victims of hunger do not choose their fate: they are civilians trapped by inhumane strategies.
Hunger is not just a medical problem: it is an ethical and geopolitical issue. Using it as a weapon is a flagrant violation of international humanitarian law. It is a slow form of extermination, a war crime, and the international community cannot turn a blind eye. There can be no peace without food justice. There can be no humanity while a single child dies of hunger as a deliberate consequence of conflict. In the face of this tragedy, silence is not neutrality: it is complicity.
Wars shrink the pie for the 99%, yet increase the portions of pie for the 1%. While parts of the world are suffering the bombs, the bullets, as well as hunger, thirst, darkness and despair, the "civilized Country's are in tandem are facing increasing Hunger for clean, healthy foods, thirst for uncontaminated water, facing calls of coming energy shortages and the darkness of despair all these things bring. Revolutionary - the Pursuit of ways to Heal and Not Steal increasing a pie for all.
Do Ye supple NAD