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

by Jason Fung

EMERGING HALLMARKS

In 2011, Hanahan and Weinberg updated their review, adding two emerging hallmarks and two enabling characteristics, that is, traits that make it easier for cancer cells to attain their hallmarks.

The first enabling characteristic is genome instabili...

The second enabling characteristic is tumor-promoting inflammation.

Hallmark 7: Deregulating Cellular Energetics

For every glucose molecule, you can generate eighteen times more energy with mitochondrial OxPhos compared to glycolysis.

Because of this increased efficiency, normal cells almost always use OxPhos if sufficient oxygen is available. But cancer cells, strangely, do not.

Cancer cells, almost universally, use the less efficient glycolytic pathway even in the p...

This metabolic reprogramming occurs in about 80 percent of cancers and is known as the Warburg effect.

Because the Warburg effect (aerobic glycolysis) is less energy efficient, cancer requires far more glucose to sustain metabolism.

Radioactively labeled glucose is injected into the body, and cells are given time to take it up. A scan reveals those areas that take up glucose more briskly. These “hot spots” are evidence of cancer activity.

This is a highly intriguing paradox. Cancer, which is growing rapidly, should require more energy, so why would it deliberately choose the less efficient pathway of energy generation? This is an utterly fascinating anomaly.

Hallmark 8: Evading Immune ...

The immune system actively seeks out and destroys cancerous cells. For example, the natural killer cells of our normal immune system constantly patrol the blood, on the lookout for foreign...

In order to survive, cancer cells must somehow evade an immune system that has been designed to kill them. While growing inside tissue, the tumor may be somewhat shielded from the immune cell that must penetrate that tissue.

When cancer spreads through the blood, however, it is exposed directly and constantly surrounded by hostile immune cells.

DEFINING ...

these eight hallmarks can be further simplified into four (see Figure 3.1).

Something can be considered a cancer when it: Grows—it sustains proliferative signaling (hallmark 1), evades growth suppressors (2), resists cell death (3), and induces angiogenesis (5); Is immortal—it enables replicative immortality (4); Moves around—it activates invasion and metastasis (6) and evades immune destruction (8); and Uses the Warburg effect—it deregulates cellular energetics (7).

Figure 3.1: Cancer paradigm 1.0 with both causes and ...

Many people believe that we don’t know what causes cancer, but actually, we already know a great deal about it.

4 CARCINOGENS

WHAT CAUSES CANCER? That’s the million-dollar (or should I say billion-dollar?) question. Most people, including many medical professionals, would respond that cancer is caused by genetic mutations. The Mayo Clinic states bluntly on its website that “Cancer is caused by changes (mutations) to the DNA within cells.”1 This is not strictly true.

Except in rare cases, genetic mutations are the mechanism, not th...

A cell that develops a number of genetic mutations becomes a cancer. That is how it becomes a cancer. But why did it develop those mutati...

Factors that cause cancer to develop are called carcinogens, and we’ve known about them for centuries.

ASBESTOS

RADIATION

B. R. Jordan, “The Hiroshima/Nagasaki Survivor Studies: Discrepancies between Results and General Perception,” Genetics 203, no. 4 (2016): 1505–12. Figure 4.1: Excess rates of cancers among Hiroshima and Nagasaki survivors.

All life on earth is constantly exposed to naturally occurring ionizing radiation that emanates from outer space. Cells protect themselves with increased antioxidant defenses and radiation-induced apoptosis.14 When cells are irreversibly damaged by radiation, they undergo a ritualistic suicide and are removed from the body. So, let’s return to our initial question: what causes cancer (see Figure 4.2)?

Figure 4.2: Cancer paradigm 1.0 with chemical and physical causes and mechanism unknown.

We knew that certain chemical agents caused cancer. We also knew that physical agents such as radiation caused cancer (see Figure 4.2). But soon, an outlandish theory was prop...

5 CANCER GOES VIRAL

I. Magrath, “Denis Burkitt and the African Lymphoma,” Ecancermedicalscience 3, no. 159 (2009): doi: 10.3332/ecancer.2009.159. Figure 5.1: Burkitt’s African lymphoma belt.

Africa’s lymphoma belt was essentially identical to the endemic areas for malaria, yellow fever, and trypanosomiasis (sleeping sickness), all conditions spread by mosquitos. Burkitt suspected that this cancer, now renamed Burkitt’s lymphoma, was linked to an infection.

THE SPECIAL VIRUS CANCER PROGRAM

HEPATITIS B AND C

HUMAN PAPILLOMAVIRUS

HELICOBACTER PYLORI

CANCER PARADIGMS

Figure 5.2: Cancer paradigm 1.0 with chemical, physical and infectious causes and mechanism unknown.

By the 1960s, all the pieces seemed to be falling into place. We knew many of the underlying factors that cause cancer. But in considering cancer as a whole, what do these diverse factors have in common? What is the unifying mechanism? To this important question, cancer paradigm 1.0 had no answer (see Figure 5.2). But by the 1970s, a new paradigm of understanding was being constructed.

PART II CANCER AS A GENETIC DISEASE (Cancer Paradigm 2.0)

6 THE SOMATIC MUTATION THEORY THE GENETIC REVOLUTION

Familial, or inherited, cancers are relatively unusual, accounting for only approximately 5 percent of cancers, leaving the vast majority (95 percent) of cancers as sporadic mutations.

Figure 6.1: Cancer paradigm 2.0 with chemical, physical, infectious and genetic causes and gene mutations mechanism.

Given that mutations accumulate randomly, more mutations increase the risk of cancer, just as buying more lottery tickets increases the chances of winning the jackpot. The SMT suggested the following chain of events, represented in Figure 6.2:

Normal somatic cells (e.g., lung, breast, or prostate) sustain DNA damage. If the rate of DNA injury exceeds the rate of repair, then random genes become mutated. A chance mutation in a gene controlling growth (oncogenes or tumor suppressor genes) causes exuberant and sustained growth. This is an important first step toward cancerous transformation, but not the only one, because growth represents only one of many hallmarks of cancer. Other gene mutations accumulate randomly over time. When certain critical abilities (hallmarks) coalesce, the cell fully transforms into a cancer.

Figure 6.2: Acquired genetic...

The basic postulates of SMT include: Cancer is caused by acquiring multiple DNA mutations. These mutations accumulate randomly. The cells in the tumor are all derived from one original clone.