Preventing Cancer Relapse: Targeting Stem Cells with the Updated CSC Tree, Repurposed Drugs, and Natural Strategies - Independent Medical Alliance (2025)

Insights from Dr. Paul Marik and Dr. Justus Hope on the hidden drivers of cancer relapse, featuring the revamped CSC Cancer Tree and practical strategies using repurposed drugs and natural compounds.

Cancer treatment often succeeds—until it doesn’t. A tumor shrinks. A scan looks clean. The patient goes home hopeful. And then… the cancer returns, sometimes more aggressive than before. The answer lies with a small population of cells that most standard treatments ignore: cancer stem cells (CSCs). These cells not only survive chemotherapy and radiation but adapt and return, driving relapse, metastasis, and mortality.

 
Dr. Paul Marik and Dr. Justus Hope have collaborated to highlight this critical issue, offering a free guide that explains CSCs, why conventional therapies fail against them, and how safe, affordable repurposed drugs and natural compounds can target them for long-term remission. This guide builds on earlier work, including the CSC Cancer Tree from Dr. Hope's 2020 book, *Surviving Cancer, COVID-19 and Disease: The Repurposed Drug Revolution*, now given a fresh makeover by Dr. Marik and the Independent Medical Alliance (IMA).

Download the free guide and read on for a summary of what’s inside.

The Cancer Epidemic: Why We’re Not Winning

“We’re currently facing a cancer epidemic. Despite billions spent and new technology, cancer rates continue to rise—up 17% in the last decade, with deaths increasing by 5%.” – Dr. Paul Marik Despite decades of research and over $200 billion spent annually, cancer rates are climbing:- 

• 17% increase in cancer cases over the past 10 years. -
• 5% increase in cancer deaths despite “advancements in treatment”. -
• 66% of patients suffer severe financial hardship due to cancer treatment costs.

Studies in *JAMA Oncology* and *Future Oncology* reveal that many new FDA-approved cancer drugs extend survival by just a few months—often as little as 3.4 months. If oncology is advancing, why the lack of progress? A key reason: treatments overlook cancer stem cells. The timing for addressing this is urgent. Cancer is overtaking heart disease as the leading cause of death, with a dramatic uptick in cases linked to factors like spike protein toxicity. Using the CSC model, we now have an opportunity to intervene and prevent recurrences after remission. Read more: $14 Billion Later, Cancer Is Worse Than Ever

What Are Cancer Stem Cells?

The concept of Cancer Stem Cells (CSCs) was first discussed publicly by Dr. Marik in early 2025 during his [CHD.TV Cancer Care Update](https://live.childrenshealthdefense.org/chd-tv/events/trending-news-segments/cancer-care-update-paul-marik/). He also covered it in his [Cancer Care](https://imahealth.org/research/cancer-care/) monograph.

CSCs are the “master” cells that give rise to the tumor. They’re not just part of the cancer—they *are* the cancer. These cells:- 

• Self-renew and multiply indefinitely. - 
• Resist chemotherapy, radiation, and immune attacks. - 
• Hide in the body and reactivate months or years later. - 
• Seed new tumors and drive metastasis.

Often comprising just 1% of the tumor, they’re the critical 1% that matters most for long-term outcomes.

The CSC Cancer Tree Gets a Makeover

For those familiar with the CSC Cancer Tree from Dr. Hope's 2020 book, there's exciting news: Dr. Marik and the IMA artists have given it a makeover. The original 2020 tree illustrated key CSC pathways and blockers. The updated version improves on this, reaching a wider audience and supporting a paradigm shift in cancer care. This revamp helps spread awareness to patients and oncologists, promising better clinical outcomes. It's Dr. Hope's dream that all cancer patients take CSC blockers post-treatment. The most effective agents for blocking major CSC signaling pathways are detailed in the IMA's resources. God bless Dr. Paul Marik and the IMA for their brave, lifesaving work and collaboration in advancing CSC awareness and research.

The Top 10 CSC Blockers and Repurposed Drug ApproachesWhich drugs or supplements, at what dosages, should physicians prescribe to suppress CSC growth and maximize chances for long-term remission? The IMA's resources (3) provide details, including evidence-informed rankings and protocols for limited and aggressive therapies. Highlights include:

Limited Therapy Approach

• Low carbohydrate, Low Glycemic diet: Include broccoli sprouts 2–3x per week; brewed green tea (<4 cups/day)
• Ivermectin: 0.2–0.4 mg/kg/day (0.3 mg/kg/day)
• Doxycycline: 50 mg daily with 2 g oral vitamin C
• Vitamin D + K2: Vitamin D 10,000 U daily + Vitamin K2 100 µg daily (monitor levels)
• Curcumin extract: 2–4 g/day, titrate up to 8 g/day
• Melatonin: 20 mg at night (titrate from 5 mg)
• Propranolol: 10–40 mg twice daily
• Resveratrol: 500 mg twice daily
• Green tea extract (EGCG): <800 mg/day

Aggressive Therapy Approach

• Low Glycemic “ketogenic” diet: —
• Ivermectin: 0.4–0.8 mg/kg/day, up to 1 mg/kg/day if needed
• Mebendazole: 200 mg daily
• Doxycycline: 50 mg daily with 2 g oral vitamin C
• Vitamin D + K2: As above, titrate per Coimbra Protocol
• Curcumin extract: High bioavailability, twice daily
• Metformin: 500–1000 mg twice daily
• Green tea extract (EGCG): <800 mg/day
• Propranolol: 10–40 mg twice daily
• Melatonin: 20 mg at night
• Resveratrol: 500 mg twice daily
• Modified Citrus Pectin: 14.4 g/day
• Sulforaphane: From broccoli seeds
• Omega-3 fatty acids: 2–4 g/day
• Atorvastatin or Simvastatin: 40–80 mg daily (monitor LDL)
• Quercetin: 500–1000 mg twice daily

The goal is to block CSC self-renewal and metastasis while minimizing side effects, with rankings based on CSC pathway blocking and safety.

Targeting the 10 Deadliest Cancers

Among the most aggressive cancers are pancreatic, small-cell lung, glioblastoma, liver (HCC), acute myeloid leukemia, esophageal, stomach, ovarian, mesothelioma, and gallbladder cancers. (4) These activate metabolic pathways like the Warburg Effect for rapid growth and resistance. Strategies include:

• HIF-1 and VEGF Blockers: EGCG, resveratrol, curcumin, metformin.
• c-Myc and GLUT1 Inhibitors: EGCG, quercetin to cut off sugar supply.
• Warburg Effect Inhibitors: Curcumin, IV vitamin C, EGCG, metformin, atorvastatin.
• Ivermectin: For common cancers to overcome resistance and suppress metastasis.

Cancer-specific protocols tailor these for types like breast, prostate, colorectal, and the deadliest ones, emphasizing stage-based care.

Pancreatic cancer 

Pancreatic cancers have significantly worse outcomes than most other types of cancer. 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 is estimated at less than three months. Unfortunately, many of the repurposed drugs are not active against pancreatic cancer cells. The drugs listed below reportedly have activity against pancreatic cancer cells.; this list is an adaption of the Bigelsen Treatment Protocol. 

1. Curcumin 

2. High dose vitamin D3 (Coimbra protocol) 

3. Doxycycline plus vitamin C 2g (PO) 

4. Ivermectin (start dose at 1 mg/kg and increase as tolerated) 

5. Metformin 

6. Atorvastatin/Simvastatin 

7. Propranolol 

8. Modified citrus pectin 

9. Mebendazole 

10. Vitamin D 

11. High dose IV vitamin C (50- 75g) together with standard chemotherapy (gemcitabine and capecitabine) 

12. Hydroxychloroquine 200-400 mg day; max dose of 5 mg/kg/day to reduce retinopathy risk. Regular eye exams are recommended to detect early signs of retinal toxicity.

Gastric Cancer 

The prognosis for gastric cancer varies significantly based on several factors, including the stage at diagnosis, the location of the tumor, and the patient's overall health. The prognosis is best for localized cancers, with a 5-year relative survival rate of about 75%. For regional cancers, the rate drops to around 35%. 

1. Atorvastatin 

2. Ivermectin 

3. Curcumin 

4. Metformin 

5. Modified citrus pectin 

6. Resveratrol 

7. Vitamin D 

8. Mebendazole

Glioblastoma 

Glioblastoma continues to be one of the most challenging malignancies to treat, with median survival typically around 12-15 months despite aggressive standard therapies. The concept of drug repurposing offers a promising approach to enhance conventional treatments by targeting resistant cell populations, particularly cancer stem cells that contribute significantly to treatment failure. Several repurposed agents demonstrate synergistic effects with standard GBM treatments. The evidence from various studies indicates that many of these agents work through distinct yet complementary mechanisms that could collectively enhance treatment outcomes. Because GBM is a very aggressive tumor with an exceedingly poor prognosis we would suggest combining all the repurposed drugs listed below together with conventional therapy. 

1. Curcumin 

2. Doxycycline plus vitamin C 

3. Metformin 

4. Resveratrol 

5. Melatonin 

6. Mebendazole 

7. Sulforaphane 

8. Propranolol 

9. Ivermectin (See paragraph below for more) 

10. Vitamin D 

11. Atorvastatin/Simvastatin 

12. Zinc (30mg day) 

13. EGCG

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 and potential for enhanced delivery through combination approaches. 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.

Triple Combination Synergy Assessment 

Based on available in vitro evidence, the triple combination of modified citrus pectin, PD-1 inhibitors, and ivermectin would likely demonstrate substantial synergistic anti-cancer activity in GBM. While each agent has individual activity or paired synergy, the combined approach addresses multiple complementary pathways that could overcome the complex immunosuppressive mechanisms in GBM. It should be noted that there is no clinical data to support this combination.

Repurposed drugs for patients with established stage 4 metastatic disease. 

1. Doxycycline (up to 200 mg/day) plus vitamin C 

2. Ivermectin 

3. Mebendazole 

4. Curcumin 

5. Metformin 

6. Resveratrol 

7. EGCG 

8. Atorvastatin/Simvastatin 

Based on the cumulative evidence from preclinical studies and limited clinical data, the likelihood of this combination arresting progression and potentially reversing metastatic cancer would be moderate to substantial. Several factors support this assessment: 

1. The combination targets multiple hallmarks of cancer simultaneously, including CSC pathways, metastatic processes, and the tumor microenvironment. 

2. Multiple agents in this combination have demonstrated synergistic effects with conventional chemotherapeutics, potentially enhancing treatment efficacy. 

3. Several of these compounds preferentially target CSCs, which are implicated in treatment resistance and disease recurrence. 

However, important limitations must be acknowledged. The majority of evidence comes from preclinical studies rather than randomized clinical trials. Stage 4 cancer is highly heterogeneous, and response may vary significantly based on cancer type and individual patient factors. The specific combination of all agents has not been systematically studied for potential interactions.

Preventing cancer progression from carcinoma in situ (stage 0 cancer) 

1. Doxycycline plus vitamin C 

2. EGCG 

3. Mebendazole 

4. Resveratrol 

5. Ivermectin 

6. Metformin 

7. Sulforaphane 

8. Curcumin 

9. Propranolol 

10. Modified citrus pectin

Repurposed drugs to treat Lymphoma (adjunctive treatment) 

1. Atorvastatin 40-80 mg daily 

2. Metformin 500-1000 mg twice a day 

3. Propranolol 10-40 mg twice a day, increase the dose as tolerated 

4. Mebendazole 100 mg twice daily 

5. Vitamin D 10 000 U daily and Vitamin K2 100 ug (monitor 25-OH Vit d and PTH levels). Titrate to achieve a low normal PTH level (Coimbra Protocol) 

6. Curcumin (high bioavailable) 2-4 g/day 

7. Green tea (EGCG) extract twice daily (< 800 mg/day) 

8. Quercetin 500 -1000 mg twice daily 

9. Ivermectin 0.4 mg/kg – 1 mg/kg daily 

Repurposed drugs to treat Multiple Myeloma (adjunctive treatment) 

1. Atorvastatin 40-80 mg daily 

2. Metformin 500-100 mg twice daily 

3. Clarithromycin 500 mg twice daily in 28-day cycles (cycled with adjunctive therapy) 

4. Celecoxib (Celebrex) 100 mg twice/day. Avoid in patients with established ischemic heart disease. Check for drug interactions 

5. Mebendazole 10 0mg twice daily 

6. Propranolol 10-40 mg twice a day, increase the dose as tolerated 

7. Curcumin (high bioavailable) 2-4 g/day 

8. Green tea (EGCG) extract twice daily (< 800 mg/day) 

9. Resveratrol (high bioavailable) 500mg twice day 

10. Ivermectin 0.4 mg/kg – 1 mg/kg daily

Acute Myeloid Leukemia (AML) – Pediatric (no radiation and standard chemo) 

1. Resveratrol 

2. Ivermectin 

3. Curcumin 

4. Doxycycline/Vitamin C (oral) 

5. Metformin 

6. EGCG 

7. Omega 3 

8. Sulforaphane

Sarcomas 

Sarcomas are cancers that arise from connective tissues such as bone, muscle, fat, and blood vessels, and usually have a poor prognosis for several key reasons: 

• Late diagnosis 
• High drade and aggressiveness 
• Large tumor size 
• Metastasis at diagnosis 
• Tumor location 
• Incomplete surgical removal 
• Tumor heterogeneity 
• Resistance to conventional therapy 

Evidence strongly supports that sarcomas typically demonstrate the metabolic reprogramming characteristic of the Warburg effect; this contributes to their aggressive growth and provides potential therapeutic targets in their glycolytic pathways. While the prognosis of sarcomas is exceedingly poor and there is limited data on the use of repurposed drugs, the following is suggested as adjunctive therapy.

• Propranolol (particularly for angiosarcomas) 
• EGCG 
• Curcumin 
• Vitamin D 
• Mebendazole 
• High dose IV vitamin C

Cautions & Contraindications

While these repurposed drugs and compounds are powerful, they require monitoring. Always consult your physician:

• Curcumin: May increase bleeding risk; stop before surgery. Caution with anticoagulants, antiplatelets, or NSAIDs. 
• Doxycycline: Minimal microbiome impact, but consider long-term use carefully. 
• Green Tea Extract (EGCG): Risk of hepatotoxicity; keep below 800 mg/day, ramp slowly, take with food (± vitamin C). Avoid in liver disease; do not combine curcumin with piperine. Monitor liver function tests (LFTs). 
• Metformin + Berberine: May cause hypoglycemia; monitor or adjust doses.
• Zinc (in Prostate Cancer): Low doses helpful early on, but avoid high-dose or long-term use, as it may increase risk and aggressiveness.
• Statins: Avoid long-term or sharp LDL drops due to dementia risk.

Conclusion

The approach emphasizes personalized, evidence-based strategies to prevent relapse. By targeting CSCs with this updated framework, we can move beyond temporary remissions toward true cures. Share these resources and join the shift in cancer care.

Sources:

1. https://imahealth.substack.com/p/targeting-cancer-stem-cells-the-key.
2. https://justusrhope.substack.com/p/the-csc-cancer-tree-gets-a-makeover.
3. https://imahealth.org/approach-repurposed-drugs-for-cancer/
4. https://imahealth.org/how-to-stop-the-10-deadliest-cancers/

Editors' Note:

These articles by the Independent Medical Alliance (previously FLCCC) offer a compelling, evidence-informed perspective on why cancer often relapses and how targeting CSCs with affordable options could improve outcomes. They are particularly valuable for patients seeking integrative approaches or clinicians open to repurposed drugs, backed by free resources and expert collaboration. However, readers should consult professionals before adopting recommendations, as these are not substitutes for personalized medical advice.