The Cancer Code: A Revolutionary New Understanding of a Medical Mystery

by Jason Fung

The human body contains more than two hundred types of these specialized cells, which are broadly classified into five categories: epithelial tissue, connective tissue, blood, nervous tissue, and muscle.

But this new complexity demanded new rules of multicellular cooperation. When grouped together, individual cells must learn to live and work together just as individual people in large cities do.

Single-Celled Organism Single Person Multi-celled Organism Multi-Person City Priority Individual Entire organism/city Modus Operandi Competition Cooperation Figure 11.1: Contrasting behavior of single-celled and multi-celled organisms.

These cell-level differences between single-cell and multicell organisms manifest in several important ways: growth, immortality, movement, and glycolysis.

G...

Immortality

Single-cell organisms are immortal because they can replicate infinitely. There is no limit to how many times a single-cell organism like yeast can divide.

For example, there are sourdough yeast starters that are more than a hundred years old that are still used to make bread.2 The yeast grows and replicates indefinitely as long as ...

Cell lines in a multicellular organism are not allowed to live forever. Each time they replicate, their telomeres get a little shorter, and when they are at a critical length, the cells can no longer divide. At that point, the cell line has reached senescence. Decrepit cells...

Movement

Glycolysis

Energy generation evolved in three stages: glycolysis, photosynthesis, and oxidative metabolism.

Earth’s early atmosphere was largely devoid of oxygen (anaerobic conditions), and thus the earliest evolved form of energy generation was glycolysis. This process breaks down a glucose molecule for two ATP and two lactic acid molecules and does not require ox...

The next major evolutionary step in energy conversion was photosynthesis, which arose approximat...

The increased availability of oxygen set the stage for the evolution of the third major type of energy generation: oxidative phosphorylation, or OxPhos, using the mitochondrion.

OxPhos burns glucose with oxygen to provide thirty-six ATP per glucose, a massive upgrade from the two ATP produced by glycolysis.

OxPhos is almost universally used in modern human cells when ...

While most single-cell organisms use the more primitive glycolysis, most euka...

So, to summarize, single-cell organisms differ from multicell organisms by these following four main characteristics: They grow. They are immortal. They move around. They u...

Does this list look familiar? It should; this is precisely the same list of attributes that make up the four hallmarks of cancer! (See Figure 11.2.) Surely this is not a coincidence. The hallmark...

Hallmarks of Cancer Unicellular Multicellular Grow Yes No Immortal Yes No Move Yes No Glycolysis (Warburg) Yes No Figure 11.2: Hallmarks of cancer, unicellular and multicellular organisms.

SPECIALIZATION

Cancer shifts away from specialized function and toward pure reproduction and growth. Normal breast cells are specialized to make milk when needed. A breast cancer cell, for its part, is not primarily concerned with milk production, but with growth of more breast cancer cells. A colon cancer cell no longer concerns itself with absorption of nutrients, but is concerned mainly with its own growth and replication.

AUTONOMY

HOST DESTRUCTION

The lone survivalist may or may not care for his surrounding environment. He may dump garbage in the river, to be carried away and become somebody else’s problem.

Cancer cells, like unicellular organisms, are locally destructive. A cancer will grow at the expense of its neighbors, destroying any surrounding tissue. The worse it is for its neighbors, the better it probably is for the cancer.

As in a society, cells in a multicellular organism must be good neighbors. Multicellular organisms must maintain the extracellular environment (called the extracellular matrix) so as not to harm their neighbors.

EXPONENTIAL GROWTH

INVASION INTO NOVEL ENVIRONMENTS

COMPETITION FOR RESOURCES

GENOMIC INSTABILITY

Microorganisms often elevate their rate of genetic mutation in response to stress using complex mechanisms such as aneuploidy,3 slipped-strand mispairing, polymerase slippage, gene amplification, deregulation of mismatch repair, and recombination between imprecise homologies.4 These processes sound complex because they are. The point is that necessity is the mother of invention: single-cell organisms find ways to increase mutation rates when needed.

Cancer, as has been painstakingly noted, is also full of genetic mutations. Cancer can mutate its genes better than almost anything else in existence.

For single-cell organisms, and cancer cells, the ability to mutate is a good thing; for multicellular organisms, it is a bad thing.

At the Cellular Level Multi-Celled Organism Cancer Cells Single-Celled Organism Priority Organism Cell Cell Modus Operandi Cooperation Competition Competition Growth No Yes Yes Immortality No Yes Yes Movement No Yes Yes Glycolysis No Yes Yes De-Specialization No Yes Yes Autonomy No Yes Yes Host Destruction No Yes Yes Exponential Growth No Yes Yes Invasion/Novel Environments No Yes Yes Competition for Resources No Yes Yes Genomic Instability No Yes Yes Figure 11.3: Behavior of multi-celled organisms, cancer cells and single-celled organisms.

Trait Infection Cancer Heart Disease Invade tissue? Yes Yes No Metastasize? Yes Yes No Develop resistance? Yes Yes No Develop genetic mutations? Yes Yes No Evolution of cells? Yes Yes No Secretion? Yes Yes No Figure 11.4: Traits of infection, cancer and heart disease.

This paradigm of cancer as an invasive protozoan explains why cancer resembles an infection much more closely than other human diseases such as heart disease.

THE EVOLUTIONARY PARADIGM

Cancer originates from cells of a multicell organism, but it behaves precisely as a single-cell organism. This is...

At long last, we have a new answer to the age-old question: what is cancer? The conventional answer from cancer paradigm 2.0 had long been that cancer is a cell with randomly accumulated genetic mutations. But Davies and others saw...

Figure 11.5: Cancer paradigm 3.0 with reversion to unicellular existence as the cause of genetic mutations.

The city dweller and the lone survivalist in the woods may appear to be completely different, but really, they are similar, just facing different situations. In the woods, people compete. In the city, people cooperate.

But what happens in a city when law and order break down? The city dweller acts more and more like the survivalist. The problem is n...

Cancer is the breakdown of multicellula...

The seeds of cancer are therefore contained within every cell of every multicellular animal. The origins of cancer lie in the origins of multicellular life on earth itself.

But how did that cell, originally part of the multicellular community, change its behavior to that of a single-cell organism? Only one force in the biological universe has that power. Evolution.

12 TUMORAL EVOLUTION

Changes in a population through selection, whether artificial or natural, have two prerequisites: genetic diversity and selective pressure.

The soil determines which seeds will flourish.