FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, August 2, 2025

Rethinking Cancer from the Roots: A Root Cause Analysis and Integrative Orthomolecular Perspective on Rasnick's The Outsider's Advantage

By Richard Z. Cheng, M.D., Ph.D.

The Chromosomal Imbalance Theory of Cancer:
The Autocatalyzed Progression of Aneuploidy is Carcinogenesis,
by David Rasnick, PhD

David Rasnick, PhD-biochemist and long-time scientific dissident-has written a bold and timely book that challenges the molecular dogmas dominating modern cancer research. In The Outsider's Advantage: A Personal Odyssey into the Essence of Cancer, Rasnick revives and expands the chromosomal imbalance theory of cancer, first proposed by Theodor Boveri in 1914 and later advanced by his colleague Peter Duesberg.

With intellectual clarity and personal conviction, Rasnick builds a persuasive case that chromosomal instability (aneuploidy) is the driving force behind cancer's many hallmarks: uncontrolled growth, metastasis, heterogeneity, and drug resistance. His book is a significant and long-overdue critique of the mutation-obsessed gene theory that has, for decades, guided a largely unsuccessful pharmaceutical assault on cancer.

As practitioners and researchers within Integrative Orthomolecular Medicine (IOM), and metabolic oncology, we strongly resonate with Rasnick's call to re-examine cancer's true origins. However, from our clinical systems biology lens, we view chromosomal imbalance not as a root cause, but as a mechanism-a downstream event resulting from deeper toxic, dietary, infectious, and nutritional triggers.

🔍 Root Cause vs. Mechanism: A Clarifying Framework

Rasnick argues that aneuploidy initiates cancer. The IOM framework, however, draws a sharper distinction between root causes (upstream initiating factors) and mechanisms (how disease unfolds).

🧬 Mechanisms (Secondary)

From the IOM view, many widely promoted theories are valid mechanisms, but incomplete explanations. These include:

1. Somatic Mutation Theory (SMT):
   Cancer is caused by accumulated mutations in DNA (1).
   ➤ Mechanism only; mutations result from deeper cellular stressors.
2. Aneuploidy / Chromosomal Instability:
   Unbalanced chromosomes disrupt regulatory pathways (2).
   ➤ As Rasnick argues, this explains heterogeneity, not initiation.
3. Warburg Effect / Mitochondrial Dysfunction:
   Cancer cells rely on glycolysis despite oxygen availability, a phenomenon first described by Otto Warburg in the 1920s. More recently, Dr. Thomas Seyfried has advanced this theory, emphasizing mitochondrial dysfunction as a metabolic origin of cancer (3,4).
   ➤ Important metabolic shift; triggered by toxins, nutrient loss, hypoxia.
4. Cancer Stem Cell Theory:
   Tumor-initiating cells drive growth, relapse, and resistance (5).
   ➤ Emerges in toxic, immune-suppressed environments.
5. Chronic Inflammation & Immune Escape:
   Sustained inflammatory signaling and immune failure promote tumor growth (6).
   ➤ Common mechanism fueled by diet, microbiome damage, toxic load.
6. Epigenetic Dysregulation:
   Gene expression is altered without mutations (7).
   ➤ Highly responsive to environmental and nutritional inputs.
7. Tissue Organization Field Theory (TOFT):
   Cancer arises from disrupted tissue microenvironments (7).
   ➤ Important systems-level insight, but not upstream enough.
8. Viral / Oncogenic Infections:
   Certain viruses can trigger oncogenesis via inflammation or insertion (8).
   ➤ Virus expression is modulated by host immunity and nutritional state.
9. Adaptive / Clonal Evolution Model:
   Cancer cells evolve under selection pressure (9).
   ➤ Descriptive of progression, not a root cause.
10. Systemic Disruption Cluster:
    This group includes downstream mediators of cancer progression that are frequently observed in modern lifestyles and environments:
    • Microbiome Disruption / Dysbiosis / Gut Barrier Breakdown (10,11): Loss of microbial diversity or integrity of gut lining, often due to antibiotics or poor diet.
      ➤ Mechanism, not root cause; arises from upstream dietary toxins, environmental exposures, and medical interventions.
    • Oxidative Stress, Metabolic Dysfunction, Immune Suppression, and Endocrine/Circadian Disruption
      ➤ All are mechanisms, not root causes; they result from upstream factors such as poor diet, toxins, infections, and medical interventions (12).

🚨 Root Cause Analysis (RCA): What Really Initiates Cancer?

IOM identifies the following as the true upstream drivers of cancer initiation:

These root causes disrupt foundational biological systems-undermining mitochondrial energy production, redox homeostasis, cellular metabolism, gene regulation, DNA repair, and immune surveillance. This breakdown creates a permissive environment for downstream mechanisms such as aneuploidy, somatic mutations, metabolic dysfunction, and uncontrolled cellular proliferation.

✅ Strengths of Rasnick's Contribution

• Reintroduces chromosomal instability as a central-but underrecognized-driver of cancer behavior.
• Exposes the failures of mutation-targeted cancer therapy and the biases of pharma-driven oncology.
• Aligns with OMNS values of evidence-based skepticism, patient-centered inquiry, and systems-level thinking.
• Calls for a rethink of cancer as a systemic disorder, not a linear gene defect.

🧠 Conclusion

Chromosomal imbalance is a key mechanism-but not the root cause-of cancer. From an Integrative Orthomolecular Medicine (IOM) perspective, upstream triggers like environmental and dietary toxins, infections, and nutrient deficiencies must be addressed if we are to truly prevent and reverse cancer.

The Outsider's Advantage is a courageous, intellectually rigorous, and deeply personal challenge to conventional cancer orthodoxy. It deserves to be read, debated, and expanded-especially by those seeking a truly integrative, root-cause model of cancer care.

🔬 Integrating the Mitochondrial Metabolic Theory of Cancer: A Unified Therapeutic Vision

In my view, the mitochondrial metabolic theory of cancer best explains the full spectrum of cancer phenomena-from the Warburg effect and immune evasion to genomic instability and metastatic behavior. This theory, championed by Thomas Seyfried and others, positions mitochondrial dysfunction-not nuclear mutations-as the central hub from which downstream chaos emerges.

However, we must be precise: mitochondrial dysfunction, while likely the key mechanism of cancer development, is still a mechanism-not a root cause. This distinction matters greatly.

We must ask the deeper question: What initiates mitochondria to fail in the first place? What disrupts their energy production, genomic stability, and signaling roles?

The answer lies in upstream root causes-the initiating insults that damage mitochondria over time:

• Environmental toxins (e.g., heavy metals, pesticides, EMFs)
• Dietary insults (e.g., seed oils, excess glucose, processed foods)
• Micronutrient deficiencies (e.g., magnesium, vitamin C, selenium, B vitamins)
• Chronic infections and inflammation
• Hormonal and circadian disruption
• Medical iatrogenesis (e.g., antibiotics, immunosuppressants, chemotherapy)

A truly integrative cancer therapy must therefore go beyond targeting cancer metabolism. It must also identify, address, and correct these most upstream root causes if we are to meaningfully prevent, reverse, and ultimately cure cancer.

This dual-level approach-correcting root causes while targeting key mechanisms-is the foundation of Integrative Orthomolecular Medicine (IOM) and the future of cancer care.

About the Author

Richard Z. Cheng, M.D., Ph.D.

Editor-in-Chief, Orthomolecular Medicine News Service
Expert Medical Reviewer, South Carolina Board of Medical Examiners
Fellow, American Academy of Anti-Aging Medicine (A4M)
Hall of Fame Inductee, International Society for Orthomolecular Medicine (ISOM)
Co-Founder, China Low Carb Medicine Alliance
Founding Organizer, Society of International Metabolic Oncology (SIMO)

Dr. Cheng is a U.S.-based, NIH-trained, board-certified specialist in integrative cancer therapy and anti-aging medicine, with active medical practices in both the United States and China. He is internationally recognized for advancing Integrative Orthomolecular Medicine (IOM)-a root-cause-driven model that combines orthomolecular nutrition, functional diagnostics, and metabolic therapies to prevent and reverse chronic disease.

A leading voice in global health reform, Dr. Cheng also serves as a medical educator, international health consultant, and public advocate. His clinical work emphasizes science-based, patient-centered care using nutritional therapeutics, low-carbohydrate interventions, and high-dose vitamin protocols to restore and sustain health.

📰 Follow his latest insights on Substack: https://substack.com/@rzchengmd

References

1. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar;144(5):646-74.

2. Duesberg P, Stindl R, Hehlmann R. Explaining the high mutation rates of cancer cells to drug and multidrug resistance by chromosome reassortments that are catalyzed by aneuploidy. Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14295-300.

3. Seyfried TN. Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer [Internet]. 1st ed. Wiley; 2012. Available from: https://www.amazon.com/Cancer-Metabolic-Disease-Management-Prevention/dp/0470584920/ref=sr_1_2?ie=UTF8&qid=1530141787&sr=8-2&keywords=cancer+as+a+metabolic+disease&dpID=51cvadUl5zL&preST=_SY291_BO1,204,203,200_QL40_&dpSrc=srch

4. Warburg O. On the origin of cancer cells. Science. 1956 Feb 24;123(3191):309-14.

5. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001 Nov;414(6859):105-11.

6. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010 Mar 19;140(6):883-99.

7. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer. 2004 Feb;4(2):143-53.

8. zur Hausen H. Viruses in Human Cancers. Science. 1991 Nov 22;254(5035):1167-73.

9. Nowell PC. The Clonal Evolution of Tumor Cell Populations. Science. 1976 Oct;194(4260):23-8.

10. Garrett WS. Cancer and the microbiota. Science. 2015 Apr 3;348(6230):80-6.

11. Macpherson AJ, de Agüero MG, Ganal-Vonarburg SC. How nutrition and the maternal microbiota shape the neonatal immune system. Nat Rev Immunol. 2017 Aug;17(8):508-17.

12. Ames BN. Micronutrient deficiencies. A major cause of DNA damage. Ann N Y Acad Sci. 1999;889:87-106.

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