PDF Summary:The Cancer Code, by Jason Fung

Cancer is one of the most frightening diseases in the world today; it’s deadly and often extremely hard to cure. As such, doctors and researchers have spent enormous amounts of time and money trying to figure out exactly what cancer is, how it works, and how to cure it. The Cancer Code by Jason Fung is an overview of scientists’ major discoveries about cancer, starting from ancient times and continuing to the present day. This guide will help you be more informed about this deadly disease.

Fung divides research trends into three different models of cancer, explores the strengths and weaknesses of each model, and discusses their implications for future cancer research and treatment. Our commentary will expand on some of Fung’s key ideas, offer counterpoints to others, and suggest some other books for further reading on this complex topic. We’ll also examine the current effectiveness of a number of cancer treatment methods and what recent discoveries might imply about future treatment options.

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Fatal Flaws of Model 2

Fung says that Model 2, while technically accurate, still fails to explain what cancer really is. It’s like trying to understand how a tree grows by cataloging every leaf on it—we’d learn a lot about individual leaves, but very little about how and why the tree itself grows. More to the point of cancer research, we wouldn’t learn anything about how to stop or reverse the tree’s growth.

Indeed, despite scientists mapping hundreds of cancer genomes, finding countless cancer-related mutations, and promising personalized treatment that targeted each patient’s specific form of cancer, a 2018 study found that less than five percent of cancer patients benefited from treatments targeting specific mutations. In other words, decades of research and billions of dollars in funding had failed to produce results.

(Shortform note: As a counterpoint to Fung’s pessimism here, in The Emperor of All Maladies, physician Siddhartha Mukherjee tells us that cancer death rates in the US decreased by an unprecedented 15% between 1999 and 2005. By 2018, they had decreased by 30%. So, while attempts to develop personalized and targeted treatments mostly failed, the knowledge that researchers gained during that time had an enormous impact on the fight against cancer.)

In addition to failing as a basis for treatment, Fung says that Model 2 also fails as an explanation of cancer. The somatic mutation theory can’t explain why cancer is so common, or why there are so many different types of cancer that all share the same characteristics.

The odds of numerous specific mutations—uncontrolled growth, hiding from the immune system, leeching the body’s nutrients, and so on—all arising in a single cell are incredibly low. Therefore, random chance can’t explain why cancer is so prevalent among modern-day humans.

(Shortform note: If it’s statistically impossible for random mutations alone to cause cancer, why did it take so long for researchers to reject the somatic mutation theory? In The Structure of Scientific Revolutions, Thomas Kuhn explains that anomalies—scientific observations that the current paradigm fails to explain—are often ignored since scientists are hesitant to reject old, established knowledge. In this case, some argue that scientists have in the past ignored or misinterpreted data that contradicts the somatic mutation theory. This includes a study that found that nearly all of the same somatic mutations occur in people with and without cancer, casting doubt on the assumption that these mutations are the primary cause of the disease.)

Model 3: Cancer as an Evolving Species

Having dismissed both of the previous models, Fung presents a newer hypothesis. Model 3 was not proposed by a biologist, but by physicist Paul Davies, whom the National Cancer Institute reached out to in 2009 in the hope that an outsider’s viewpoint could provide some new insights about cancer.

Model 3 suggests that cancer is an atavism: an evolutionary throwback in which ancestral traits reemerge in modern organisms. In this case, Davies proposed that cancer is the re-emergence of traits from the earliest single-celled organisms, caused by evolutionary pressure from carcinogens. (We’ll explain this evolutionary pressure in more detail later.)

In short, Model 1 described what cancer is, Model 2 described how it works, and now Model 3 offers a theory about why it happens.

(Shortform note: In The Selfish Gene, biologist Richard Dawkins gives an idea of what these earliest organisms might have been like. He describes simple molecules that gained the ability to replicate themselves using resources in the environment. Eventually, those easily-available resources were depleted and the replicator molecules needed to compete with each other. As a result, they evolved traits like protective protein membranes, as well as more efficient ways to find and consume nutrients so they could continue replicating themselves. In short, they became simple—but fully functional—self-contained organisms.)

Support for Model 3

To support this idea of cancer-as-atavism, Fung points out that cancer cells act like simple organisms: They grow, feed, reproduce, and evolve. Therefore, rather than Model 2’s concept of random mutations causing cells to run wild, this hypothesis says that cancer’s behavior is actually extremely logical and focused on survival; not the survival of the host, but of the cancerous “organism.”

(Shortform note: At the beginning of The Selfish Gene, Dawkins gives a biologist’s answer to the age-old question of why life exists: to survive and reproduce. Model 3 is suggesting that’s exactly what cancerous cells are doing—surviving and reproducing by any means necessary. That’s why Fung says they behave like organisms.)

Atavism explains why cancer can be found in nearly every animal species on Earth: It’s because the traits of cancer come from our oldest common ancestors. Furthermore, there’s genetic evidence for this theory in addition to the behavioral evidence—mutations in cancerous cells are most likely to affect those genes that evolved shortly after the first multicellular organisms emerged, effectively reverting them to the genes of single-celled organisms.

(Shortform note: The human genome contains an incredible amount of what, until recently, scientists called “junk DNA”—genetic material that doesn’t seem to serve any purpose. While we’ve recently discovered that some of this DNA does serve a purpose within the body, that “junk” also includes pseudogenes, which scientists believe are essentially evolutionary leftovers. In other words, pseudogenes are broken or suppressed copies of genes that our ancestors carried. Model 3, cancer-as-atavism, could mean that some of those suppressed genes are reactivating.)

In other words, malignant cells didn’t need to evolve cancerous traits from scratch, because the genes for the traits were already in their DNA. The cells just needed to evolve (or devolve) in such a way that those genes reactivated.

A New Model, or Corrections to An Old One?

While Fung presents Model 3 as a revolutionary new understanding of cancer, we could also see it as simply an updated version of Model 2. To illustrate this point, Thomas Kuhn’s The Structure of Scientific Revolutions says that there are two ways science progresses:

Method one: puzzle-solving. This is part of what Kuhn refers to as “normal science,” where scientists steadily build upon our existing knowledge. They may find the need to make minor corrections, but it isn’t necessary to completely overturn our current understanding of the topic.

Method two: revolution. This happens when scientists find something that the current model can’t explain, and a minor correction isn’t sufficient. For example, when astronomers found that the Earth-centric theory of the solar system couldn’t predict the movements of stars and planets—no matter how much they tweaked the theory and played with the numbers—it eventually became clear that the opposing Sun-centric theory was more accurate.

In this case, Fung presents the Atavistic Theory of cancer as a revolution, overthrowing the established Somatic Mutation Theory. In reality, the Somatic Mutation Theory wasn’t wrong, just incomplete; cancer is the result of mutations, but those mutations are less random and less extreme than scientists previously thought. That solves the puzzles of why cancer is so common and why different forms of cancer have such strong similarities.

How Model 3 Fixes Model 2

Fung says that this model of cancer as an evolving species solves the two major shortcomings of the somatic mutation theory. First, cancer does not spring up at random—the elements of cancer are already present in our DNA, so all the cell needs to become malignant is for those genes to reactivate. This provides a much more satisfactory answer to cancer’s prevalence than random chance could.

Second, Model 3 reveals that genetically-targeted treatments are mostly ineffective because of cancer’s genetic variation. After turning cancerous, cells continue to divide and mutate extremely quickly, meaning that even cancerous cells within a single patient can have countless different genetic traits. So, while a targeted treatment will kill many of the malignant cells, it’s very likely that some will be resistant to it. Even worse, those surviving cells will continue to reproduce, meaning that cancer can evolve to resist any given treatment.

Therefore, to cure a patient and avoid relapse, doctors must either find and target the root mutation—the original genetic change that all the cancer cells share—or use a battery of different treatments to ensure that every malignant cell is destroyed.

Counterpoint: Model 3 Isn’t Totally New

To pose a partial counterpoint to Fung, doctors have known for decades that not all cancer cells respond to treatment the same way and that multiple treatment methods are much more effective than any single targeted treatment.

In The Emperor of All Maladies, Mukherjee describes a number of advancements in treatment that took place in the 1950s and early 1960s. Doctors found that using cocktails of multiple chemotherapy drugs worked significantly better than any single drug and that using radiation therapy in conjunction with chemotherapy further increased the treatment’s effectiveness. They also found that, for a patient to be truly cured without relapsing, every trace of cancer had to be wiped from that patient’s body.

So while doctors might not have been thinking of cancer as its own species, they certainly knew that it had genetic variation, as well as the ability to reproduce and adapt, and they treated the disease accordingly.

How Model 3 Describes the Progression of Cancer

Using this new model of cancer as a separate species, Fung describes how the disease progresses in three phases:

Phase 1: Carcinogens Drive Cellular Evolution

We mentioned before that there are countless known carcinogens, and that carcinogens cause damage that the body sometimes repairs incorrectly. However, Fung says that viewing cancer as an evolving species provides a more complete explanation of how carcinogens work: carcinogens create evolutionary pressure at the cellular level.

Every known carcinogen causes some kind of damage—the sun damages your skin, tobacco smoke damages your lungs, and so on. The damage isn’t serious enough to kill every cell the carcinogen reaches, but it does kill some of them, leaving the surviving cells to reproduce. The cells most likely to survive are those with the traits of cancer: rapid reproduction, the ability to ignore signals that trigger cell death, the ability to co-opt the body’s resources for their own survival, and so on.

In short, cells evolve cancerous traits because they’re very effective survival mechanisms.

Evolution: Survival of the “Good Enough”

If we consider cancer as an independently evolving species, it might seem strange that it would evolve in such a way as to kill its host (and therefore itself). However, evolution isn’t intelligent and it doesn’t plan ahead; it simply means organisms that are able to survive and reproduce in their current environment will do so.

While evolution is commonly framed as survival of the fittest, some biologists argue that it would be more appropriate to call it survival of the adequate. In other words, evolution doesn’t try to create some hypothetical perfect organism (for instance, a cell that could survive carcinogens without turning malignant); it’s the process by which “good enough” organisms create more “good enough” organisms.

In short, carcinogens create an environment where cells with cancerous traits have significant advantages over cells without those traits. The fact that those malignant cells might kill their host years down the line is irrelevant—they’re able to survive and reproduce, and therefore, they do so.

Phase 2: Growth Factors Drive Cellular Reproduction

Growth factors are naturally-occurring chemicals and proteins that, as the name suggests, stimulate cell growth and cell division. Every multicellular organism needs growth factors; however, since rapid cell growth is the primary hallmark of cancer, growth factors create an ideal environment for cancerous cells to flourish. More cells also mean more mutations—more genetic diversity—which helps to prepare the cancerous “species” for the next step in its evolution.

The body’s growth factors are controlled by nutrient sensors that detect the presence or absence of various nutrients in the body. When nutrients are plentiful, the growth factors activate; when nutrients are scarce, the growth factors deactivate so the body can focus on conserving energy and culling damaged cells.

(Shortform note: Interestingly, while Fung says Model 3 proves that genetically-targeted cancer treatments won’t work, others believe that discoveries about how cancer grows and feeds could provide exactly the sort of genetic targets researchers have been looking for. Specifically, if cancer cells all use the same kinds of nutrient sensors and growth factors, then developing a way to disrupt that process—for example, with a drug that binds to a nutrient sensor and blocks it—could allow doctors to “starve” the cancer and kill it, hopefully with minimal side effects to the patient.)

According to Fung, growth factors and nutrient sensors explain why cancer is so much more prevalent in Western countries: Our diets contain a lot of processed foods with easily-accessible nutrients, meaning those growth factors are almost always active. As a result, our bodies create cells more rapidly and destroy mutated cells more slowly than usual.

With this in mind, Fung suggests that reducing our consumption of processed foods and intermittent fasting can help to prevent cancer by reducing growth factor activity. He puts particular emphasis on controlling our insulin levels; eating a lot of simple sugars causes the body to produce a lot of insulin, which acts as a growth factor and increases the likelihood of cancer.

(Shortform note: Fung is a nephrologist—a kidney doctor—with a particular interest in dietary health and metabolic diseases such as type 2 diabetes. Therefore, not surprisingly, he spends a great deal of time discussing the possible connections between diet and cancer. However, except for certain types of meat, there’s little scientific evidence that any particular dietary factors increase the risk of cancer. Currently, the only commonly accepted connection between diet and cancer is that obesity is associated with increased cancer risk.)

Phase 3: Metastasis Drives Further Evolution

As a cancerous tumor grows, it also metastasizes. This means that the tumor sheds cells into the blood, where they are carried to different parts of the body. Those cells invade tissue in other places and give rise to new, secondary tumors.

However, Fung says that the process of metastasis is more complicated than many people think. The cells shed by the primary tumor face enormous evolutionary pressures: First of all, the immune system will find and destroy most of these cells while they’re still in the blood. Then, those few that can evade the immune system are still unlikely to survive—for example, a cancer cell that evolved in the liver wouldn’t be well suited to grow in the stomach.

Therefore, rather than simply spreading out from the primary tumor, metastasis can be a circular process. Malignant cells—further evolved from the evolutionary pressures they faced while traveling through the body—sometimes return to that first tumor and reattach to it in a process called tumor self-seeding. Now, these new cells must compete with the original cancer for resources; only the cells that reproduce most quickly and invade other tissues most effectively will survive.

Over numerous cycles, this process eventually gives rise to cells that are strong and aggressive enough to survive in other parts of the body, and those are the cells that go on to form secondary tumors. In other words, cancer doesn’t just fight against the body’s defenses; it’s in constant competition with itself to produce the hardiest and most virulent organisms possible.

Treatment Implications of Self-Seeding

As it turns out, cancer cells don’t return to the original tumor simply by chance; one study observed that tumors send out chemical signals encouraging circulating cancer cells to reseed it. That same study found that—as Fung says—self-seeding increases how quickly cancer grows and how effectively it performs other functions like angiogenesis.

As with every new discovery about how cancer grows and develops, doctors are hopeful that the discovery of self-seeding will provide new opportunities for targeted treatments, allowing them to fight cancer more effectively and with fewer harmful side effects. By preventing self-seeding, it may be possible to slow or even stop cancer’s growth and spread throughout a patient. It should also prevent local tumors from reappearing after surgical removal, as commonly happens with breast cancer.

Treatments Based on Model 3

Fung says that this new understanding of cancer—as an independent, evolving species—may represent a turning point in the fight against it. With a better understanding of how cancer operates and how the body fights against it, there is hope for more effective treatments with fewer side effects.

One promising option is immunotherapy: activating and strengthening the patient’s natural immune response. Fung points out that cancer doesn’t simply overwhelm our body’s defenses like a deadly infection does; instead, it evolves methods to hide from those defenses.

Therefore, forcibly activating the immune system and teaching it to target cancer cells—essentially, giving the patient a “cancer vaccine”—is highly effective. Furthermore, regardless of how the malignant cells continue to mutate, the immune system will still recognize them as foreign and destroy them.

(Shortform note: Immunotherapy is currently used as a cancer treatment, with mixed results. Depending on the type of cancer, immunotherapy drugs are effective in anywhere from 20% to 50% of cases. One study found that immunotherapy increased the five-year survival rate of a certain type of lung cancer from 5.5% to 15%. In short, immunotherapy can be effective, but it doesn’t seem to be the type of silver bullet that Fung implies it could be.)

Another strategy Fung discusses is adaptive therapy, developed by oncologist Robert Gatenby. Adaptive therapy uses standard chemotherapy treatments, but it aims only to keep the cancer at a manageable level instead of wiping it out entirely. This goes against the currently accepted practice of subjecting cancer patients to the strongest doses of drugs and radiation that they can withstand.

Gatenby’s reasoning is that the usual approach to chemotherapy creates extremely strong evolutionary pressure; if any malignant cells survive, they’re sure to be the ones most resistant to treatment, and those cells then pass their resistance on to a whole new generation of cancer.

Therefore, he believes that lower, less frequent doses of chemotherapy will be more reliable in the long run—there will be less pressure for the cancer cells to develop resistance to the treatment. Furthermore, drug resistance is costly in evolutionary terms; in the absence of those drugs, the cells without such resistances will be more successful. In this way, adaptive therapy seeks to turn cancer against itself by allowing the non-resistant cells to outcompete the resistant ones, then introducing another round of chemotherapy to beat them back.

While cancer is unlikely to be eliminated completely by such a strategy, Gatenby hopes that it will keep the disease stuck at an easily-managed level. This could allow more cancer patients to live longer and more normal lives than current chemotherapy methods provide.

(Shortform note: In Gatenby’s paper proposing adaptive therapy, he also said that, in some cases, he was able to achieve a stable tumor size with decreasing chemotherapy doses and increasing intervals between treatments. In other words, far from evolving resistance to chemotherapy, the cancer was actually becoming more vulnerable to it as non-resistant cells repeatedly outcompeted resistant ones. Gatenby, while acknowledging that this is a very early result and that his method needs a great deal more study, said that his results suggest adaptive therapy could eventually cure some cancers entirely—the disease would reach a point where all of the malignant cells are susceptible to chemotherapy, and would be wiped out by the next treatment.)

These methods represent a major change from previous strategies, which unknowingly played to cancer’s greatest strengths: reproduction and evolution. Currently, the favored strategy is to simply blast away at the disease with toxic drugs and radiation until nothing remains, but even this approach requires doctors to overcome cancer’s constant replication and mutation—not to mention the devastating side effects the treatment regimen has on the patient.

Fung believes that, with this new model of cancer as an evolving species, there is hope for the future of cancer treatment. He acknowledges humanity still has a long fight ahead of it, but he says we’ve started gaining ground in that fight for the first time.

(Shortform note: Even with all of these new discoveries and theories, developing treatments for cancer is a slow and expensive process. New drugs require numerous studies for effectiveness and safety before they can even be tested on humans, and even then, clinical trials must be done carefully and under strict regulations.)