Theory of Cancer

The prevalent understanding of cancer progression, known as the driver mutation or somatic mutation theory, asserts that cancer arises when cells acquire many genetic mutations that promote abnormal growth and behavior. These mutations, termed "driver mutations," are believed to be the main factors responsible for the conversion of normal cells into cancerous ones.

However, recent research is increasingly scrutinizing this mutation-focused viewpoint. New studies indicate that merely accumulating mutations does not fully explain the intricate process of carcinogenesis. Instead, it is becoming evident that mutagenesis may interact with various biological mechanisms, including epigenetic alterations, metabolic changes, and disturbances in the tumor microenvironment, to initiate and facilitate cancer development. Here's my thesis:

A fundamental characteristic of cancer cells is their inclination toward anaerobic respiration leading to the conversion of glucose into lactic acid instead of carbon dioxide {ref}. This is known as the Warburg Effect.

Elevated lactic acid and inflammation promote each other in a malicious cycle {ref}. The onset and progression of inflammation can be triggered by a variety of factors: chronic stressors that may have contributed to the development of cancer {ref|ref|ref|ref|ref|ref|ref}, the tumor itself, the body’s response to the tumor, or cancer treatments (surgery, RX, chemotherapy). Additionally, dietary, lifestyle and environmental factors are contributing factors. 

Incessant inflammation results in increased expression of HIF1α {ref|ref} which further stimulates the glycolytic process, causing the production of more lactate contributing to persistent and increasing sub-toxic ammonia levels.

Before the Great Oxygenation Event (GOE), the atmosphere had very little oxygen. Instead, the atmosphere contained elevated levels of ammonia {ref}, an important energy source for one-celled organisms, such as bacteria and yeast.

Cancer cells tend to thrive in environments low in oxygen, which resemble the anaerobic environment of Earth before the GOE. Under these conditions, ammonia acts as a signaling molecule that triggers cellular growth and division {ref}. An increase in the amount of ammonia in tissues and a decrease in the ability of the body to excrete it raises lactic acid and interferes with oxygen uptake {ref}. This, in turn, leads to hypoxia and produces a shift towards glycolysis, perpetuating the deadly cycle. 

Therefore, I propose that cancer is a metabolic disruption, and ammonia is its catalyst and energy source.

 

Hypothesis: ammonia is the catalyst of cancer development

The conventional theory of cancer: a genetic disease

Cancer cells have gene mutations and will unceasingly continue to replicate. Gene mutations can be either inherited or acquired.

Examples of inherited mutations:

• Hereditary breast-ovarian cancer syndrome
• Lynch Syndrome
• Li-Fraumeni syndrome
• Cowden syndrome

Acquired: dysregulation of more than 700 genes at multiple steps in cell signaling pathways.

Cancer beyond the traditional genetic framework

Metabolic, evolutionary, environmental, and even psychological factors that might contribute to cancer development.

Cancer, a metabolic disease

Can cancer metabolism be targeted to stop cancer proliferation?

According to San-Millán and Brooks GA "Lactate is probably the only metabolic compound involved and necessary in all main sequela for carcinogenesis, specifically: angiogenesis, immune escape, cell migration, metastasis, and self-sufficient metabolism. We hypothesize that lactogenesis for carcinogenesis is the explanation and purpose of the Warburg Effect. Accordingly, therapies to limit lactate exchange and signaling within and among cancer cells should be priorities for discovery".

"Warburg, Koch, and Szent-Gyorgyi had a comprehensive view of biology, in which the aerobic production of lactate, resulting from a respiratory defect, itself was functionally related to the nature of cancer." - Ray Peat, Ph.D. (1936-2022).

Cancer, an evolutionary throwback (atavistic reversion theory)

Cancer tumors are able to survive with very little oxygen, this supports the idea that cancer emerged when the amount of oxygen in the atmosphere was extremely low when life first appeared on our planet.

Suggested treatments:

• Increase oxygen in the body
• Focus on the immune system, help trigger the patient's own immune system cells to attack cancer

If cancer is part of the history of the cell and for whatever reason the cell reverted to that ancient function, trying to forever halt cancer via metabolic pathways as mentioned above, seems to be a near-impossible task to accomplish since many cancer cells will survive the most inhospitable and nutrient-deficient conditions.

As for the reason, could it be that a normal cell becomes cancerous because of adaptation? Is the cell trying to adapt or cope with a changing habitat e.g. less oxygen, more ammonia, etc.? So the cell activates genes that a billion years ago were an efficient mechanism to deal with such an environment.

Theory of Cancer Stem Cells (CSC)

The cancer stem cell hypothesis proposes that tumors are comprised of a heterogeneous cell population, with only a subset of cells being responsible for the initiation, maintenance and progression of the disease. This subset of cells, referred to as cancer stem cells (CSCs), are thought to be responsible for the aggressiveness of tumors and may be resistant to chemotherapy and radiation. CSCs are believed to possess several key characteristics, such as self-renewal, tumor-initiating ability and the ability to differentiate into other cancer cell types.

{overview}

Cancer is a wound that does not heal.

Chronic irritation theory. {Ref}

Wound Healing Produced by Cartilage Preparations

Dr. John Prudden’s 31 Cases: Treating Cancer with Bovine Tracheal Cartilage. "Dr. John F. Prudden (1920-1998), found that bovine tracheal cartilage had a powerful and consistently positive effect on wound healing, arthritis, cancer, and other diseases."

Oxygen, pH, Lactate, and Metabolism—How Old Knowledge and New Insights Might Be Combined for New Wound Treatment

Melancholy as a risk factor for cancer

{historical overview}

Depression and the Immune System: A Close Connection {Ref}

Cancer is caused by nutritional deficiencies.

This thesis challenges the prevailing understanding of breast cancer causation by proposing that it may primarily be a deficiency disease, caused by the lack of a specific protective agent found in varying amounts in food, and ultimately, soil. {ref}

Cancer cells that arise from bacteria

BOCC hypothesis {Ref} ⟹  It's the Terrain. 

Evidence supporting this hypothesis

1. There are 10× more bacterial cells than human cells in the human body.

2. Bacteria play a key role in carcinogenesis. 

3. Like bacteria and single-celled eukaryotes (protists, e.g., yeast), cancer cells can grow in agar medium and form colonies, proliferate in the absence of anchorage in vitro, and ferment glucose in the absence of oxygen (anaerobic fermentation) with the production of lactic acid.

4. Cancer cell genomes were assembled from DNA fragments all at once in a single catastrophic event (chromothripsis).

5. Cancer cell genomes contain bacterial DNA.

6. Genes of ancient and unicellular origin are highly and preferentially expressed during tumorigenesis.

Cancer is a consequence of an acidic body and lymphatic obstruction.

Robert Morse, ND - The Acid Alkaline Balance

Cancer is a delayed severe hypersensitivity reaction.

Reviewing a large body of evidence on many chronic inflammatory diseases and carcinogenesis the author proposes that cancer is a severe form of hypersensitivity responses (immune disorder) in site-specific tissues resulting from the accumulation of exaggerated expression and co-expression of immune responses and the creation of a molecular immune tsunami, primarily in the immune-responsive tissues. {ref}

Cancer is first of all a cachexia accompanied by a tumor.

It is proposed here that carcinogens deplete a vital substance and induce a metabolic deficiency that ends in cachexia. To survive, the organism grows a protective organ-the tumor-that replenishes the missing substance. {Ref}      

Cancer is caused by a loss of efficient use of oxygen.

Oxygen-Starved Tumor Cells Have Survival Advantage That Promotes Cancer Spread {ref}

Stem-like cancer cells grow more rapidly under hypoxic conditions {study}. 

{ref/ref}

Dysregulation of the urea cycle

Cancerous tumors disrupt the urea cycle, a process in the liver that breaks down nitrogen waste. This disruption allows tumors to hoard nitrogen, a crucial building block for DNA and RNA, thus fueling tumor growth. {ref}

Cancer is the result of a homeostatic imbalance.

About the intricate relationship between the body's natural state of equilibrium (homeostasis) and the development of tumors and their subsequent spread (metastasis). It emphasizes that cancer is not simply uncontrolled cell growth, but rather a breakdown in the delicate balance between cell growth and cell death.

{ref}

Cancer is caused by sulfate deficiency.

The author claims that sulfate deficiency is a critical driver of various health issues, including cancer. She emphasizes the crucial role of sulfate in numerous bodily functions, particularly in the vasculature and cell function. She proposes that tumors, rather than being inherently harmful, actively work to alleviate the problems caused by sulfate deficiency.  {ref}  

The Cell Competition Theory of Cancer

This thesis proposes that cell competition plays a crucial role in both promoting and suppressing tumor formation. They show how mutations in YAP, KRAS or Pten can elevate cell fitness, and therefore, tumor cells harboring these mutations (winner) can outcompete wild-type parenchyma (loser). Inducing these mutations in the liver parenchyma is sufficient to trigger the opposite situation; cancer cells (loser) are eliminated by liver parenchyma (winner). {ref}