What I've Been Reading

Unicellular genes that enhance competition and survival are precisely those genes that cause cancer in multicellular organisms. The seed of cancer already exists in every multicellular organism, because it is simply a remnant of our evolutionary past. When the new rule break down, the old unicellular behaviors reassert themselves. The seed of cancer grows, is immortal, moves around, and uses the Warburg effect. This is an ancient tool kit of survival responses. These are the hallmarks of cancer. This is the new invasive species known as cancer. 

The Cancer Code: A Revolutionary New Understanding of a Medical Mystery by Dr. Jason Fung.

Dr. Jason's book was published few months after Max passed away but until I read this book, I have no idea that cancer is a unicellular organism that was competing with Max and every one of us who are multicellular organisms. This changes everything I knew about cancer and the treatment options. To be clear, none of the treatments given to Max nor available now are nothing but playing Russian roulette with not only genetics, lifestyle, ecology but against a primordial unicellular organism which is evolved before we did. 

What is Cancer?

The term cancer does not refer to a single disease, but denotes a collection of many different diseases related to certain qualities. Something can be considered cancer when it has the following 8 characteristics:

• Grows
• It sustains proliferative signaling
• It evades growth suppressors
• It resists cell death
• It induces angiogenesis.
• Is Immortal
• It enables replicative immortality
• Moves Around
• It activates invasion and metastasis
• It evades immune destruction
• Uses the Warburg Effect
• It deregulates cellular energetics

Benign cancer shares all the first five characteristics and without the ability to metastasize, cancer is more a nuisance than a serious health concern. 

Somatic Mutation Theory (SMT)

The basic postulates of SMT include: 

1. Cancer is caused by acquiring multiple DNA mutations.
2. These mutations accumulate randomly.
3. The cells in the tumor are all derived from one original clone. 

The somatic mutation theory of carcinogenesis patched together all the disparate know causes of cancer into a coherent, unified theory (mine: very similar to a religious, free-market, or soviet style ideologies).  This paradigm focused research from extrinsic agents (chemicals, radiations, and viruses) onto intrinsic defects (genetic mutations). 

The great contemporary thinker and philosopher Nassim Taleb often uses this allegory of the Procrustean bed to describe how facts are often tortured to fit a certain narrative. The widely and often blindly followed somatic mutation theory of cancer required a Procrustean bed to fit the facts, too. 

Cancer was far, far more different genetically than they were alike since:

• Different types of cancer had different mutations 
• The same type of cancer in different patients had different mutations. 
• The same cancer in the same patient had different mutations in the primary tumor compared to metastatic cancer. 
• The same cancer in the same patient had different mutations in different mutations at different sites of metastasis. 
• The same cancer in the same patients in the same tumor mass had different mutations. 

Cancer was a baffling mishmash of genetic peculiarities that had almost no connection to one another. Genetic mutations were everywhere and nowhere. Some cancers had hundreds of mutations, and others had none at all. The rate of mutations necessary to develop a cancer is much higher than the known rate of mutation in human cells. Normal cells just don't mutate anywhere close to the rate needed to produce cancer. Finally, the genetic mutations were a proximate, rather than a root, cause of cancer. 

Genetic mutations may explain the mechanism of how cancers keep growing, but they do not explain the fundamental question of why these genes mutated. The SMT fails because it is entirely inward-looking, towards our genes, instead of outward-looking, toward the environment. The seed is important, but the soil matters most. 

Cancer is older than humanity

The oncogenes and the tumor suppressor genes discovered so laboriously over the last quarter-century are mutations of normal genes. Every single cell in our body contains the seed of cancer. Why?

Dogs get cancer. Cats get cancer. Rats get cancer. Even the most primitive multicellular organisms develop cancer. In 2014, cancer was discovered in two species of hydra. You may recall from high school biology class that hydra are simple, small aquatic organisms that evolved very early on from single-cell organisms. 

The origins of cancer are found at the origins of all multicellular life itself. This may have seemed obvious to a cancer outsider, but not to an insider with the curse of knowledge. Cancer is very deeply embedded into the way multicellular life is done. 

Cancer is older than humanity. Searching for the answers to cancer's origin among the evolutionarily recent genes of humans is futile. The answers are simply not there. Cancer was something much older and more fundamental to life on earth than humanity. 

Single-cell organisms differ from multicellular organisms by the following four main characteristics: 

1. They grow
2. They are immortal
3. They move around
4. They use glycolysis (also called the Warburg effect)

These are precisely the characteristics of cancer!

Cancer originates from cells of a multicellular organism, but it behaves precisely as a single-cell organism. This is a spectacular and novel finding. 

The roots of cancer lie in our evolutionary past. Perhaps cancer was not a forward-looking evolutionary process, but a backward-looking one. 

Today's standard cancer treatments resemble ancient existential threats: radiation (pre-ozone layer), poison, and antimetabolites (nutritional challenges, periodic starvation). Unicellular cells are no strangers to these threats and have evolved effective responses to flourish under these precise conditions. 

We've long treated cancer as some kind of random genetic mistake. A mistake that arises in all animals throughout history and evolves independently in millions of people a year? Cancer is hardly a mistake. Cancer is the ultimate survivor. When all else dies, cancer is there because it is the core of the cell that will survive at all costs. Cancer is not random, and it is not stupid. It has developed the tools it needs to survive. 

This model fits the known facts of cancer better than any previous paradigm. Undoubtedly, this will not be the final word on cancer, and it should not be judged as such. Nor are all its suppositions proven facts. There will always be much to learn about cancer, but I believe this new paradigm is a huge and useful step forward, explaining many of cancer's mysteries. 

Nutrition & Cancer: 

Fiber - By comparative study between African (with lots of fiber) and Western diet (little fiber); cancer was not simply a disease of too little fiber, and thus, eating more fiber didn't translate into less cancer. 

Fat - By comparative study between South Pacific Islanders (with lots of fat) and Indian vegetarians (low fat); lowering dietary fat resulted in no measurable protection against cancer. 

Vitamins - When vital nutrients like beta-carotene are available in large doses, cancer cells are highly active and grow like weeds. Same with folic acid (vitamin B9), Vitamin E while Vitamin C, D, and Omega-3 oils were neutral. High-dose vitamins promote cell growth. It is really that simple. 

But diet plays a large role in cancer. 

• Obesity clearly increases the risk of cancer. Obesity also clearly increases the risk of type 2 diabetics. The link - insulin. 
• Avoid - Sugar and refined grains which leads to hyperinsulinemia. 
• Insulin is an important nutrient sensor, signaling the presence of food, but what does that have to do with cancer? Everything! The nutrient sensor insulin is also a highly potent growth factor. 
• Each increase in ten centimeters in height is associated with a 16 percent increase in the risk of cancer. Growth factors increase height. Growth factors also increase cancer risk. 
• The most widely studied natural food for cancer chemoprevention (term used to denote foods, supplements, or drugs that may block progression of cancer) is green tea, which contains high levels of catechins. 

Growth - The common thread that runs through all conditions of increased weight, increased weight, increased eyeball length (myopia), and cancer is that they are all conditions of excessive growth. We often think growth is good, but the truth is that in adults, growth is not necessary or even good. Quite the contrary, growth is bad, sometimes very bad. 

Mammalian target of rapamycin (mTOR) - This was an astonishing revelation for biologists - the equivalent of discovering a new continent in the Atlantic Ocean. Hundreds of years of medical science had somehow missed this fundamental nutrient-sensing pathway that was so essential to life on earth that it had been conserved in animals from yeast all the way to humans. In an evolutionary sense, mTOR is older even than the much better-known sensor insulin. The mTOR pathway is found in virtually all life-forms, rather than just mammals, so the name was changed to a mechanistic target of rapamycin, but it retained its catchy moniker "mTOR". 

AMPK - The nutrient sensors insulin and mTOR respond mainly to dietary intake of carbohydrates and proteins. The nutrient sensor AMPK, however, assesses the overall available cellular energy. 

• Lots of energy stored = low AMPK
• LIttle energy stored = high AMPK
• High AMPK lowers mTOR activity, slowing growth down. AMPK increases the production of new mitochondria, the energy makers in cells, to increase the cell's capacity for burning fat. AMPK also increases autophagy, the important cellular self-cleansing, and the recycling process. 
• Foods and drugs that activate AMPK - Diabetes drug metformin; resveratrol from grapes and red wine; epigallocatechin gallate (EGCG) from green tea and chocolate; capsaicin from peppers; turmeric, garlic, and the traditional Chinese medical herb berberine. Calorie restriction also activates AMPK. 

Autophagy - The word autophagy derives from the Greek word auto, meaning "self" and phagein, meaning "to eat", so it literally means "eating oneself". Autophagy is a regulated, orderly process of degrading cellular components to be recycled into new ones. Autophagy functions as a cellular housekeeper, when mTOR is high, putting the cell into growth mode, so autophagy and mitophagy (the process of removing old and damaged mitochondria) turn off. 

• Nutrient deprivation, especially protein deprivation lowers mTOR and activates autophagy. 

Metastasis:

Cancer cells break off the primary tumor to find more room to grow. This happens early in cancer's course, as the circulating tumor cells (CTCs) consume nutrients rapidly and are very quickly driven by the increased competition for resources. This new environmental stress creates new evolutionary selection pressures. 

Unfortunately, these CTCs find out that the bloodstream is a terribly hostile environment, and most just die. One day, a rare genetic mutant arises that is able to survive both the immune cell attack and the travel through the bloodstream long enough to circulate back to the original tumor site. 

As it returns home, it finds a sanctuary against all the scary things trying to kill it, and it recovers. The tumor has just self-seeded. But this returning cancer is more aggressive and just a tiny bit better able to survive in the bloodstream. This more aggressive variant multiplies within the safety of the primary tumor site. It dominates and outcompetes the incumbent cancer cells. This cycle of tumor self-seeding and metastasis repeats over and over, with cancer continually evolving over time its ability to survive the bloodstream. 

Eventually, a rare genetic mutation allows the cancer cells to reach the new distant shore of the other organs and manage to survive. They might not thrive, but at least they're not dead. This micrometastasis is so small that it is undetectable and may lie dormant for decades. Invasion and metastasis are difficult to skills to master, and most cancers fail. 

Given enough time, Darwinian evolutionary processes select a rare genetic variant to flourish, and the little outpost of metastatic cancer cells grows. Cancer has just become metastatic. This slow process from initial carcinogenesis to metastasis takes decades. 

New Dawn:

The evolutionary/ecologic paradigm recognizes the importance of cell-to-cell interactions and interactions with the environment, making it a far more dynamic, inclusive, and comprehensive theory of cancer. Evolutionary biology links carcinogenesis, progression, and metastasis, whereas genetics considers them all as separate issues. 

This idea is not new; it just needed to be rediscovered. "Cancer is no more a disease of cells than a traffic jam is a disease of cars," wrote cancer researcher D.W. Smithers in 1962. A traffic jam results from the interaction between the car, neighboring cars, and the environment. If you look only at each individual car - Are the brakes working? Was it recently serviced? - you will fail to find the problem. 

Similarly, cancer is not only a genetic disease but also an ecological disease. The environment plays a huge role in determining whether cancer grows. Under certain conditions, such as high insulin levels, cancer will thrive, while under other conditions, it will fail to establish itself. 

Treatments:

Screening

Simply catching more early-stage diseases is not useful by itself. In breast and colorectal cancer, screening reduced late-stage disease but in prostate, esophageal, and pancreatic cancer it has not, and that makes all the difference in the world. 

Many of the early-stage breast cancers are unlikely to ever progress to a dangerous state - as the evolutionary model explains, cancer can be fully contained by the body's own anti-cancer mechanisms. Aggressive treatment of early cancers is simply unnecessary. With toxic treatments such as surgery, radiation, and chemotherapy, the treatment may be worse than the disease. 

Finding and treating cancers that don't need to be treated is not a useful strategy. 

Without good evidence of the benefits of screening, and a better understanding of why it may fail, we must rely on the ancient medical guiding principle of Primum non-nocere, which means, "First, do no harm." 

Dietary Determinants

Autopsy studies find unsuspected prostate cancer in 30 percent of men over the age of fifty, 50 percent by age seventy, and an astounding 80 percent by age ninety. Because the seed of cancer is ever-present in all our cells, an important question is: why don't you get cancer? If it is not a seed problem, then it may be a soil problem. Diet is a hugely important determinant of progression because nutrient availability is inextricably linked to cell growth, particularly for cancer cells. For the most part, dietary prevention of cancer boils down to one key strategy: avoiding diseases of hyperinsulinemia, including obesity and type-2 diabetes.   

Ketones

When fat is metabolized for energy, molecules called ketone bodies are produced, which cancer cells have difficulty using. By simulating the breakdown of muscle protein, amino acids are delivered to the liver and converted to glucose, which cancer cells love. So, while weight loss may be a useful strategy to prevent the progression of cancer, cancer cachexia (a phenomenon of unintentional weight loss in patients with advanced disease), once advanced, limits the effect of diet on cancer treatment. Reducing glucose in an attempt to "starve" cancer is only modestly hopeful because advanced cancer can break down other tissues to free the glucose it needs. Dietary therapy must likely be combined with other treatments to be effective at this stage.

Fasting & Cancer:

• Intermittent fasting is a promising nutritional approach for cancer prevention, as it protects against many risk factors such as obesity, type 2 diabetes, and inflammation. 
• Fasting simultaneously reduces all human nutrient sensors, most of the growth pathways, and also increases autophagy and mitoghagy. 
• Fasting during chemotherapy may also reduce the side effects of treatment while increasing efficacy. Fasting protects the normal cells by putting them into a quiescent state, or maintenance mode, which may help mitigate chemotherapy side effects of hair loss and nausea. Cancer cells do not enjoy this protective state because their genetic programming puts them into continuous growth mode. 

Immunotherapy

Immunotherapy has several inherent advantages over conventional treatments. 

• The boosted immune system is a dynamic system that can better keep pace with cancer's moves. The immune system can adjust and evolve alongside the cancer. 
• Immune system has a memory, so it may prevent recurrence. 
• Immunotherapy has fewer side effects than standard chemotherapies because the immune system is a targeted treatment. 
• Immunotherapy is a systemic treatment, which is crucial because cancer is a systemic disease. Metastasis occurs early in the disease process, so a systemic therapy can treat potential micrometastases throughout the body. The immune system can lock on and destroy cancer cells and does not need to be manually targeted in the same way as local treatments like surgery and radiation. The systemic nature of treatment also means that immunotherapy may be effective even very late in the disease process, after the cancer has metastasized.