The History And Evolution Of The Somatic Mutation Theory In Cancer

The History And Evolution Of The Somatic Mutation Theory In Cancer The consensus theory explaining the cause of cancer is called the Somatic Mutation Theory. It has guided research and treatment in cancer for over 70 years. Let's re-examine its (non) validity. Sun, 18 Aug 2024 15:30:49 GMT https://pierrekorymedicalmusings.com/p/the-history-and-evolution-of-the In this post, I plan to, as succinctly and simply as possible, introduce the two competing theories regarding the origin of cancer and then go through the evidence for the current “consensus” theory which is called the Somatic Mutation Theory or SMT. The competing theory, called the Metabolic Theory of Cancer (MOTC) will be summarized in my next post in this series.

First, let’s define cancer. From the seminal paper “Hallmarks of Cancer ” by Weinberg and Hanahan, a cell is defined as “cancerous” when they exhibit these 8 characteristics;

it stimulates its own growth

it evades growth suppressing signals

it resists cell death (apoptosis)

it enables replicative immortality

it induces the ability to grow new blood vessels to further tumor growth (angiogenesis)

it spreads to distant sites (metastasis)

it has the ability to evade the immune system

it has a “reprogramming of energy metabolism” (the “Warburg Effect)

In layman’s speak - cancer is the uncontrolled growth of a cell - ever dividing and not dying off naturally nor allowing itself to be cleared by the immune system. Plus, it allows itself to spread and then multiply in areas of the body distant from its origin (a characteristic for which no mutation has ever been found to explain this property but forgive me for I am getting ahead of myself).

Now, one of the main points of this post is that characteristic #8, that of having undergone a “reprogramming of energy metabolism” (the central pillar supporting the MOTC) was only added to the list above after one of the top SMT cancer researchers in the world was “admonished” to do so by one of the top researchers of the MOTC. Although it was added only 10 years ago, Warburg discovered this unique property of a cancer cell in 1927. Weird.

Now, to understand the core difference between the two theories you will need a simple understanding of cell biology, i.e. the basic structure and function of a cell. So, as simply as possible, know these two things about cells:

THE NUCLEUS (Central to the Somatic Mutation Theory)

What you need to know about the nucleus is:

The nucleus is generally considered the control center of the cell because it stores all the genetic instructions for manufacturing proteins used by the cell

The DNA is the blueprint of instructions that dictates everything a cell will do and all of the products it will make (the information is contained in “genes” within the DNA - short sequences of “instructions”).

When a cell divides, the DNA must be duplicated so that each new cell receives a full complement of the parent cell’s DNA

The “Somatic Mutation Theory” posits that cancer arises from the accumulation of genetic mutations (errors) in tumor suppressor or tumor promoter genes within the DNA of the nucleus, causing the aberrant behaviors listed above. These mutations are caused by various “carcinogens” (agents that cause cancer) within our environment.

THE MITOCHONDRIA (Central to the Metabolic Theory)

All you need to know about the mitochondria is:

A mitochondrion is a membranous, bean-shaped organelle that is the “energy transformer” of the cell. Each cell has numerous mitochondrion.

Along its inner membrane is a series of proteins, enzymes, and other molecules that perform the biochemical reactions that convert either oxygen or glucose into energy in the form of adenosine triphosphate (ATP), which provides usable cellular energy

Cells use ATP constantly, and so the mitochondria are constantly at work.

Oxygen molecules are required to make ATP, which is why you must constantly breathe. Converting oxygen to ATP is a process called “aerobic respiration.” There is also another, less efficient pathway that a mitochondrion can make energy by, and that is via using sugar (glucose), a process called “anaerobic respiration” or “fermentation.”

The “Metabolic Theory of Cancer” posits that carcinogens, instead of directly damaging DNA, instead first damage the mitochondria in such a way that they cannot use oxygen to create energy and are instead forced it to rely near solely on sugar (glucose) for energy

This abnormal respiration is exhibited by ALL cancer cells. The MTOC experts argue that it is this alternative energy pathway reliance by the dysfunctional mitochondria which then induce abnormal changes in nuclear function such that new mutations arise or cancer-causing genes already present are “turned on.”

An important concept to know, and which will begin to reveal my bias in support of the MOTC is that abnormal respiration is present in every cancer cell, but not every cancer cell has been found to have mutations in their DNA. Tumors free of any mutations can even possess aggressively cancerous properties.

THE HISTORY OF THE SOMATIC MUTATION THEORY (SMT)

Read more