Refining the Ivermectin Protocols for Cancer

AI Analyzes Pancreatic, Colon & GBM Cancers

Cancer Cells

Dr. Marik and I are optimistic and encouraged that we have published some basic and useful guidelines in attacking Cancer Stem Cells CSCs. This will make a huge difference in cancer survival based on extensive literature evidence coupled with AI’s processing ability. However, we are not satisfied yet.

We are constantly revising as we add additional information. Our goal is to refine these two protocols continuously and apply them to key cancers as we learn more through our ongoing joint research. We are developing cancer-specific protocols and previewing them to our readers today.

With that said, Ivermectin is becoming the foundational repurposed drug in many of our developing cancer-specific protocols.

While it may rank slightly lower down the list in specific AI searches, its broad range against multiple cancer growth targets makes it a vital agent in almost every cancer. In some, such as brain cancers, Ivermectin’s lack of crossing the blood brain barrier might - at first glance - seem to be an issue.

• However, despite this “minor” problem, I have a bombshell to release later on Glioblastoma and Ivermectin, and IVM can and does still have massive activity against this monster tumor.

Sometimes a lack of studies on a specific cancer may result in a slightly lower Ivermectin ranking. This is due to lack of data but does not mean Ivermectin wouldn’t be effective.

In addition, not asking AI the question precisely may result in a different answer, but this does not change the underlying supporting PubMed study evidence. And I save all of the underlying studies in every AI search I conduct.

• Ivermectin is the most versatile of the anti-metastatic and anti-CSC cancer agents with Curcumin being a close second.

• As I shall discuss more later, Ivermectin attacks metastases through multiple non-CSC mechanisms. For example, it is also active in immune checkpoints and cancer metabolism.

• More than 400 studies and counting have been published on Ivermectin + Cancer, and these are rapidly growing as more is discovered.

• Ivermectin is becoming and will continue to be a foundational repurposed drug against cancer. But do not expect Big Pharma to admit this anytime soon, as Ivermectin can only subtract profits from a trillion-dollar industry. This is not a political statement, but an unfortunate economic fact of life.

My father passed away 14 years ago after an 18-month battle with Pancreatic Cancer. And my friend and colleague passed away in 2024 following a 4-year struggle with Glioblastoma. My patient of 35 years is now in hospice with Colon Cancer having rejected anything to do with repurposed drugs.

I dedicate this Substack to them and will analyze these three cancers in more detail today.

I am more convinced than ever they could have been spared with an aggressive Ivermectin-based repurposed drug protocol. And AI confirms this below:

#1. Pancreatic Cancer: Cancer-Specific Cocktail

Pancreatic cancer consistently emerges as one of the deadliest metastatic tumors.

• Those with pancreatic cancer have significantly worse outcomes than most other cancer types, with a hazard ratio of 1.71 compared to cancers of unknown primary (CUP).

Nearly half (49.5%) of metastatic pancreatic cancers spread to the liver and 20.3% to the lungs.

• The median survival for patients with liver metastases from pancreatic cancer is estimated at less than three months, even with the standard of care treatments involving highly toxic chemotherapy, radiation, and in some cases, surgery.

AI’s Refined Analysis of Pancreatic Cancer:

Revised Rankings of Repurposed Agents for Pancreatic Ductal Carcinoma:

1. Curcumin

2. Doxycycline

3. Vitamin C

4. Ivermectin

5. Metformin

#2. Glioblastoma Multiforme: Cancer-Specific Repurposed Drug Cocktail

Glioblastoma GBM continues to be one of the most challenging malignancies to treat, with median survival typically around 12-15 months despite aggressive standard care.

• The concept of drug repurposing offers a promising approach to enhance conventional treatments by targeting resistant cell populations, particularly cancer stem cells CSCs that contribute significantly to treatment failure.

• Many of these agents work through distinct yet complementary mechanisms that could enhance treatment outcomes.

GBM Cancer Stem Cell Targeting Mechanisms

Cancer stem cells CSCs represent a critical therapeutic target in glioblastoma as they drive tumor recurrence and resistance to conventional therapies.

Multiple repurposed agents demonstrate significant activity against these cells through diverse mechanisms.

• Metformin, for example, has been extensively studied for its effects on glioblastoma stem cells.

• Research indicates that metformin treatment reduces the proliferation rate of tumor-initiating cell-enriched cultures isolated from human glioblastomas and impairs tumor-initiating cell spherogenesis, demonstrating a direct effect on self-renewal mechanisms.

Similarly, resveratrol potently inhibits GBM stem-like cell growth through multiple pathways, including AKT deactivation and p53 induction.

Sulforaphane, a constituent derived from cruciferous vegetables, has shown remarkable efficacy in targeting glioblastoma stem cells. Studies reveal that sulforaphane "was effective in eliminating GSCs, which play a major role in drug resistance and disease recurrence”. This ability to specifically target the stem cell population represents a crucial mechanism for preventing tumor recurrence.

Anti-Invasion and Anti-Metastatic Properties

Beyond targeting cancer stem cells, many of these agents demonstrate significant anti-invasive properties.

• Doxycycline, for instance, has been shown to decrease migration and invasion capabilities of cancer cells while inhibiting epithelial-to-mesenchymal transition (EMT), a key process in tumor invasion.

Although the primary studies focused on breast cancer cells, the mechanisms involving downregulation of stem cell factors (Oct4, Sox2, Nanog, and CD44) are relevant across multiple cancer types, including glioblastoma.

• Resveratrol specifically inhibits the invasion of glioblastoma-initiating cells via down-regulation of the PI3K/Akt/NF-κB signaling pathway.

• Another study clearly demonstrated that "resveratrol suppresses EMT and EMT-generated stem cell-like properties in GBM by regulating Smad-dependent signaling".

This multi-faceted action on both stemness and invasiveness represents a powerful approach to controlling glioblastoma progression.

Synergy with Standard Treatments

Several repurposed agents demonstrate synergistic effects with standard GBM treatments.

• Zinc has been shown to enhance the efficacy of temozolomide (TMZ), the standard chemotherapeutic agent for GBM.

Research indicates that "zinc may serve as a potentiator of TMZ therapy in GBM patients", suggesting its potential role as an adjuvant therapy.

• Mebendazole, an anthelmintic drug, has progressed to clinical trials for GBM treatment. Studies have shown that "mebendazole not only exhibits direct cytotoxic activity but also synergizes with ionizing radiations and different chemotherapeutic agents".

AI’s Recent Analysis of GBM:

Revised Ranking of GBM Repurposed Drugs for Pancreatic Cancer:

1. Metformin

2. Mebendazole

3. Doxycycline

4. Ivermectin *

5. Curcumin

6. Resveratrol

7. Sulforaphane

8. Vitamin C

   *See discussion below

#3. Colon Cancer: A Cancer-Specific Cocktail

The proposed below combination targets multiple cancer pathways simultaneously:

1. Inhibition of Metastatic Processes: Curcumin and resveratrol directly reduce the invasion and migration capacity of gastric cancer cells, while curcumin specifically reduces circulating tumor cells that are essential for metastasis formation.

2. Cancer Stem Cell Targeting: Doxycycline, mebendazole, and metformin effectively target cancer stem cells through different mechanisms, addressing the root cause of metastasis and therapeutic resistance.

3. Angiogenesis Suppression: EGCG markedly reduces tumor microvessel density and inhibits VEGF-induced endothelial cell functions necessary for tumor growth and metastasis.

4. Cell Signaling Disruption: Multiple agents (curcumin, ivermectin, metformin) disrupt key signaling pathways (PI3K/Akt/mTOR, YAP1, NF-κB) that drive gastric cancer progression.

5. Metabolic Reprogramming: Metformin and doxycycline alter cancer cell metabolism, making them more vulnerable to conventional therapies and reducing their metastatic potential.

Revised Ranking of Repurposed Colon Cancer Drugs - Based on Metastatic & CSC Blocking:

1. Curcumin

2. Metformin

3. Ivermectin

4. Doxycycline

5. Resveratrol

6. Mebendazole

7. EGCG

Summary:

Blocking CSCs is the fundamental principle behind our repurposed drug protocol.

We have already covered the pathways that our repurposed drugs block with Ivermectin at the top.

But Ivermectin is NOT designed to be a one-man band. The idea is to block as many cancer growth pathways as possible, and to attack the tumor from as many angles and variations as possible without creating toxicity. Think about the AIDS cocktails. While one drug, AZT, was not enough to stop this disease, a cocktail or drug combination worked extremely well in suppressing the disease. The same is true of cancer.

This is something the standard of care cannot do. Because multiple chemotherapy drugs are simply too toxic. And this is the reason CSCs are missed. And this is the primary cause for recurrence, metastasis, and treatment failure.

However, supplements are generally safe with the exceptions mentioned in our protocol.

Ivermectin is one of the safest drugs on the planet, even safer than many over the counter medications. Thus, a 9 or 10 repurposed drug/supplement combination works well. The idea is to have these repurposed agents work in concert with the standard cancer care usually involving chemotherapy, radiation and surgery.

Ivermectin and the “Disappearing” Metastases

But there is more. And this gets into why Ivermectin suppresses Glioblastoma growth so effectively despite our understanding that it does not cross the blood brain barrier. And this may be the secret as to why Ivermectin is so successful at creating “disappearing metastases.”

Case reports have shown that a PET scan may show total body metastatic cancer spread, while months later there is NED - no evidence of disease - after Ivermectin and repurposed drugs are added. There are other case reports showing astonishing activity against GBM.

Why?

Both Dr. Marik and I were surprised. We thought that because Ivermectin did not cross the blood brain barrier, it could not benefit a patient with GBM. Allow me to show you why it can.

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Here is the complete AI analysis.

Immune Checkpoint Blockers.

Immune Checkpoints are proteins which interfere with our normal immune function.

• When the cancer creates these Checkpoints, the tumor is allowed to grow and spread without any immune suppression, and it can devastate its host quickly through metastatic spread.

As it turns out, Ivermectin has a plethora of Natural Checkpoint Blocking activities and this can synergize with Keytruda which acts by mainly one pathway. Adding Ivermectin can synergize Keytruda and thus turn a “cold” tumor into a “hot” tumor, meaning it can take a tumor devoid of any T cells and suddenly infuse it full of T cells resulting in our immune system “eating” the now “warm" tumor, resulting in its total destruction.

A crucial study involving Ivermectin and Keytruda demonstrated the importance of our immune system in fighting cancer and reversing these checkpoints.

• A group of mice with metastatic cancer were treated with Ivermectin which by itself produced a poor response. Only 1/20 mice survived.

• Another group of mice was treated with the Immune Checkpoint PD-1 Inhibitor - Keytruda - and they fared no better. Only 1/10 survived.

• However, when Ivermectin was added to Keytruda, 6/15 mice or 40% achieved long term survival, a complete response.

  

Other compounds besides Ivermectin possess natural immune checkpoint blocking activity such as resveratrol. But when I queried AI, it could not provide another drug besides Ivermectin that could turn a cold tumor hot. Instead, AI explained that some cancer drugs could make hot tumors hotter. But none were as talented as our Ivermectin.

Here is the AI answer:

Ranking of Repurposed Drugs by Immune Checkpoint Blocking Activity:

Back to Ivermectin’s GBM Activity Despite not Crossing the BBB:

The blood-brain barrier presents a significant challenge for delivering therapeutic agents to brain tumors. However, several factors may allow Ivermectin to exert effects against GBM despite its limited BBB penetrability.

First, GBM tumors themselves disrupt the integrity of the BBB. As noted in the research, "under inflammatory conditions (such as those in GBM) these junctions are not as tightly connected making the endothelium 'leaky'". Particularly at the tumor core, GBM is associated with a weakened blood-tumor barrier (BTB) with increased permeability, potentially allowing for greater drug penetration.

Additionally, areas of GBM with high metabolic activity drive local hypoxia and trigger vascular endothelial growth factor production and angiogenesis, which involves disruption of inter-endothelial tight junctions. This process results in a weakened blood-tumor barrier with increased permeability, especially in the tumor core.

• While areas of the tumor distal from the hypoxic core may remain protected by a more intact BBB, the compromised barrier at the core could allow for some Ivermectin penetration.

Ivermectin's Immune Modulation in Cancer

Although most studies on Ivermectin's immune effects have been conducted in cancers outside the brain, they provide valuable insights into its potential immune activity against GBM. In breast cancer models, Ivermectin has demonstrated the ability to induce immunogenic cancer cell death (ICD) and promote robust T cell infiltration into tumors.

It functions as an allosteric modulator of the ATP/P2X4/P2X7 axis, which operates in both cancer and immune cells, selectively targeting immunosuppressive populations including myeloid cells and regulatory T cells (Tregs).

Perhaps most importantly for GBM applications, Ivermectin has shown the capacity to convert "cold" tumors (with little immune infiltration) to "hot" tumors (with significant immune infiltration).

This property is particularly relevant to GBM, which is characterized by substantial local immunosuppression and is often considered a "cold" tumor resistant to immunotherapy.

Potential for Enhanced BBB Penetration Under Certain Conditions

Interestingly, research suggests that Ivermectin's BBB penetration can be enhanced under certain conditions.

• A study examining the effects of whole-brain radiation therapy (WBRT) on BBB permeability found significant increases in 3H-ivermectin brain uptake 12 hours post-WBRT in immunocompetent mice. This indicates that combination approaches might increase Ivermectin's access to brain tumors.

The study observed a time- and size-dependent opening of the BBB following WBRT, which was more pronounced in immunocompetent mice compared to immunocompromised ones.

• This suggests that the immune response plays a role in the magnitude of BBB disruption following irradiation. This finding has important implications for potential combination therapies involving Ivermectin and radiation for GBM treatment.

Systemic Immune Effects Relevant to GBM

Even without complete BBB penetration, Ivermectin could exert systemic immune effects that impact GBM progression. GBM's immune evasion strategies extend beyond the local tumor microenvironment to include systemic immunosuppression6.

By modulating the peripheral immune system, Ivermectin could potentially counteract some of these systemic effects.

Ivermectin's ability to inhibit the NF-κB pathway and modulate proinflammatory cytokine production could help restore immune function even at a systemic level.

Additionally, its documented effects on myeloid-derived suppressor cells (MDSCs) could be particularly relevant, as GBM patients show elevated circulating MDSCs in their blood compared to healthy individuals.

Potential Synergistic Combinations for GBM Treatment

The most promising application of Ivermectin for GBM may lie in combination therapies. Research has shown significant synergy between Ivermectin and immune checkpoint inhibitors in breast cancer models.

• While neither agent alone showed efficacy in vivo, the combination therapy achieved synergy in limiting tumor growth and promoted complete responses.

For GBM applications, combining Ivermectin with treatments that increase BBB permeability, such as focused ultrasound or radiation therapy, might enhance its delivery to the tumor.

• Additionally, combination with established GBM treatments like temozolomide could potentially improve outcomes by targeting multiple pathways simultaneously.

The combination of Ivermectin with anti-PD1 antibodies is particularly intriguing given GBM's high expression of PD-L1, which has been linked with poorer patient survival.

• If Ivermectin can indeed convert "cold" GBM tumors to "hot" tumors as it does in breast cancer, this could potentially sensitize them to checkpoint inhibitor therapy.

WNT-TCF Pathway Inhibition: A Key Mechanism

Ivermectin also demonstrates inhibitory effects on the WNT-TCF signaling pathway, which is implicated in multiple cancers, including lung and intestinal malignancies.

In one study, Ivermectin was found to mimic the effects of dominant-negative TCF, inhibiting the expression of WNT-TCF targets.

• This mechanism may contribute to its anti-cancer properties and could be relevant to GBM treatment, as abnormal WNT signaling has been implicated in GBM pathogenesis.

At low concentrations, Ivermectin shows selective anti-WNT-TCF activities, and these effects appear to be distinct from its actions on chloride channels that mediate its anti-parasitic effects.

• This specificity suggests that Ivermectin could potentially target cancer-specific pathways without necessarily crossing the BBB in large quantities.

Conclusion

Despite Ivermectin's limited BBB penetrability, several factors suggest it may still exert immune activity against GBM. These include the inherent disruption of the BBB in GBM tumors, Ivermectin's systemic immunomodulatory effects, its ability to convert "cold" tumors to "hot" tumors in other cancer models, and potential for enhanced delivery through combination approaches.

The recent identification of Ivermectin as a potential therapeutic for GBM through gene expression analysis adds to the growing body of evidence supporting its investigation as an anti-GBM agent.

While complete eradication of GBM with Ivermectin alone is unlikely given BBB constraints, its unique immunomodulatory properties and potential synergy with other treatments warrant further exploration in preclinical and clinical studies.

The ideal approach may be to investigate Ivermectin as part of a multi-modal treatment strategy for GBM that leverages its immune-enhancing properties while addressing the challenge of BBB penetration through complementary treatments.

Given Ivermectin's established safety profile in humans, translational studies examining its effects on the GBM immune microenvironment could be pursued relatively quickly, potentially offering new hope for patients with this devastating disease.

Bonus Material - The Moss Report’s Retort

Ivermectin & Cancer: Hype vs Science - What’s the Reality?

For anyone who has watched the Moss Report hit piece on Ivermectin, please note that Dr. Paul Marik drafted a thoughtful rebuttal outlining a wealth of research supporting Ivermectin’s efficacy not only in COVID-19 but in cancer.

For those of you who have not watched the Moss Report’s Ivermectin episode, I can save you the trouble. It is definitely not hype, not with the exponential increase in Ivermectin + Cancer PubMed studies being published.

But you may find it interesting that Dr. Moss, a PhD, not an MD, promotes natural remedies and happens to be an Adviser to the NIH Alternative Medicine Department. He has not prescribed a single patient a single prescription drug in his career, yet believes he is in a position to tell patients what prescription drugs not to take for their cancers.

While he does not personally routinely take any prescription drugs as he notes in his books, he does advise everyone to keep up on their recommended vaccines. And he encourages patients to write the FDA to request they fund studies on Ivermectin and Cancer.

He states the FDA will be “sympathetic” to such requests.

And curiously after Dr. Marik posted his 200-word rebuttal to the Moss YouTube Broadcast, it was taken down within seconds according to Dr. Marik. And this happened despite multiple attempts.

Dr. Moss claims his main criticism of Ivermectin for Cancer is that the studies are mainly preclinical, and he will not take it seriously until good clinical studies become available. Furthermore, Dr. Moss does not see any compelling evidence that Ivermectin should be used by patients at this time.

However, given the fate of other repurposed drugs reviewed since 2020, it seems that these clinical studies will not be funded or accomplished any time soon.

• Moss does not believe Ivermectin should be available over the counter in any state due to potential misuse and dangerous side effects. Perhaps his efforts would be better spent doing hit pieces on Tylenol as this is far more dangerous than Ivermectin.

Moss begins his report on Ivermectin by discussing a “quack” practitioner who was arrested for selling snake oil cures.

So, with that said, here is my rebuttal for Dr. Moss - advisor to the NIH and Founder of the Moss Report. I will allow this screenshot from AI to do the talking for me.