Alternatives to the Somatic Mutation Theory

By Linda L. Isaacs, M.D.

I previously discussed some of the problems with the Somatic Mutation Theory of carcinogenesis. If you need a refresher, click here.

A critique of the Somatic Mutation Theory in the Journal of Cancer lists 15 other theories about cancer development. Much of the discussion is quite complicated, so I've listed some of the common elements of the theories. These alternatives to the Somatic Mutation Theory include some or all of the following ideas:

Genetic changes in cancer are a byproduct, not a cause

In this premise, the cell changes, and subsequently, the genetic material changes. This can happen by mutations (changes in the molecules of DNA) due to errors in the duplication process. Or, genetic material may be folded differently, or have different proteins or substances attached to the DNA. This changes how the genetic code interacts with the machinery that manages the cell.

This could explain why many of the “mutations” seen in cancer cells are also seen in normal cells. It could also explain why some “targeted” therapies, designed to affect cancer cells by interacting with the products of mutated genes, have unexpected side effects. The “mutations” may be present in normal cells and so the “targeted” medication affects those cells as well. The abnormality that the “targeted” therapy is attacking is not unique to cancer cells.

Cancer is caused by alterations in tissues

Tissues are made up of various kinds of cells, and cells influence one another’s behavior. Tissues can become inflamed, perhaps by a foreign body, an infection, poor metabolic health, nutritional deficiencies, or carcinogenic substances. Then, some cells may escape from the control of this altered cellular environment, becoming cancer cells.

Cancer cells have reverted to a more primitive,“stem-like” state

Cancer cells look and act a lot like the cells in the embryo, the earliest stage of development. Both types of cells divide rapidly, migrate, invade, and create new blood supplies. Mature cells are described as “differentiated,” cancer cells as “undifferentiated,” another way to describe an appearance closer to embryonic cells. Movement along this continuum, from differentiated to undifferentiated and back again, has been observed and can explain spontaneous remission of cancer.

For further reading, I suggest this 2025 article in PLoS Biology, The end of the genetic paradigm of cancer.

Next Section: Dr. John Beard's Theory of Carcinogenesis

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