Cancer Recurrence May Not be What You Think (what it really is and what can be done to prevent it)

I was recently talking to a friend of mine about the post-treatment anxiety felt by most cancer patients when their mind inevitably circles to the question: “Is my cancer still there, lingering, just waiting to come back?” My friend also happens to be a cancer researcher with a doctorate from MIT, and a cancer survivor. “I know my cancer is still inside me,” she told me, “That’s why I’m so selfishly motivated to find real cures.”

Doctors don’t often discuss the probability of recurrence once treatment is over, probably because in many types of cancer the statistics are depressing. Just look at breast cancer: a 2008 study conducted at MD Andersen concluded survivors of breast cancer face a 1 in 5 chance of recurrence within 10 years, even with 5 years of adjuvant therapy given to prevent recurrence.(1)

Once initial treatment is over, and patients are sent home, many speak of a lingering fear that their cancer will return. Every survivor probably deals with this in his or her own way.(2) The fear is no doubt rooted in the impression doctors and patients have of the nature of cancer — a disease they believe originates because a series of mutations permanently rewires the cell circuitry into an invasive killer — a process that once established cannot be undone, and unless every last cell is killed, the cancer will come back with a vengeance.

But is this impression correct? The only way to find out for sure is to compare the mutations found in the primary tumor against those in the recurrent tumor and see if they match. If they match, it’s almost certain to be the same cancer, if not, then it’s almost certain to be a separate case, independent of the original. A 2010 study of head and neck cancer found that 18.7 percent of recurrences within 36 months after treatment with radiation were not recurrences at all, but in fact were a completely new cancer.(3) (31.2% showed some discordance leaving it not clear if they were recurrences that had acquired new mutations or if they were new cases)

A Swedish study that followed more than 1000 women with breast cancer over a 10 year period showed that 33% of the recurrent samples contained a change in hormone receptor status and 15% had a change in HER2 status.(4)This is astounding considering doctors usually don’t retest both hormone and HER2 status upon recurrence, assuming it is still the same as the primary tumor sample, reflecting the mistaken believe cancer recurrence is alway just that, a recurrence of the initial disease.

So what does this all mean? First, it means both doctors and cancer survivors need to redefine what recurrence is. In many cases it appears that it’s not a recurrence at all, but really a new case, unrelated to the primary case. Second, the data implies that cancer treatment is often more successful than previously thought. If the “single cell hypothesis” is right — the idea that leaving even a single cell behind is enough to cause a recurrence — then the data implies treatment must often be successful, completely eradicating the disease down to the very last cell.

But if treatment completely eradicates cancers in many cases, why would new cases “recur” at such a high rate?

When my friend stated that she “knew her cancer was still inside of her,” perhaps a better way of stating it might be, “the conditions that caused my cancer the first time are still there, and there is a chance either my original cancer will return or a new case will arise.”

Recurrence makes sense from a genetic perspective if it’s a true recurrence; a reigniting of the same cancer with the same purportedly causal alterations to DNA. But that doesn’t explain recurrences where it is a genetically distinct cancer. How could a person be so unlucky twice? After all, 93% of cancers arise sporadically, the result of a very unlucky and a highly unlikely series of mutations to key genes as described by the genetic theory of cancer. This leaves many cases of recurrence looking like lightning striking in the same spot twice. In some cases the treatment itself could further this process along. Many chemotherapies are potent carcinogens, especially radiation.

The fact that many recurrences are actually “new” cases of cancer is actually a good thing. First because, as stated previously, it implies treatment is often successful. Second, it implies that there is a window of time to make the changes that might prevent a recurrence. Something within your control.

The question then becomes: how could a cancer survivor decrease the chance of recurrence?

The answer depends on the nature of cancer itself. Whether it is primarily a genetic disease or primarily a metabolic disease.

If cancer is caused by random mutations to DNA then little can be done to prevent recurrence other than avidly avoiding carcinogens. The rest is largely up to fate. But if cancer is primarily a disease of dysfunctional metabolism, as many experts are now contending, then a lot can potentially be done to prevent recurrence. (My book Tripping Over The Truth:The Metabolic Theory of Cancer, is the story of the re-emergence of the metabolic theory of cancer first purposed by German Scientist Otto Warburg in 1924)

There are many inconsistencies plaguing the idea cancer is a disease exclusively due to genetic mutations. The most obvious is that the heterogeneity observed in mutations from patient to patient is astonishing, making it very difficult to say which mutations cause cancer at all. Tumors can be found with as few as one, or even ZERO mutations, a fact that completely flys-in-the-face of an exclusively genetic origin of cancer. These facts, and many others, have forced the foremost cancer researchers to acknowledge the importance of epigenetic influences in the origin of cancer. Bert Vogelstein of Johns Hopkins, one of the most famous cancer researchers in the world, called epigenetic influences the most probable explanation for the “missing mutations” discovered in the genomes of almost every type of cancer.(5) Epigenetic influences operate outside the “fixed” genetic code and are a form of fluid, changeable, genetic expression. For example, nutritional signals cause epigenetic changes. When a person begins a ketogenic diet a host of genes get “turned on,” in order to manufacture the necessary enzymes to produce and burn ketone bodies. (Incidentally, because of their badly damaged mitochondria, cancer cells are unable to make the transition to utilize ketones as fuel)(6)

Even though there is very little consistency from one patient’s tumor to the next with regard to genetic mutations, cancer cells do have one consistent feature, badly damaged, and greatly reduced numbers of mitochondria. In fact, the aggressiveness of tumor cells correlates to the degree of mitochondrial dysfunction. When mitochondria are unable to function properly they send out an epigenetic signal to the cell’s nucleus. The signal instructs the nucleus to start manufacturing the necessary enzymes for anaerobic energy-metabolism using glucose, thus compensating for impaired aerobic energy-metabolism because of dysfunctional mitochondria. The signal does something else: it activates a series of oncogenes instructing the cell to become unhinged from the tight controls of cellular division. The result: cancer.

It is important to note that the metabolic-theory claims cancer is under epigenetic control. The genetic-theory of cancer claims it’s under the control of the fixed genetic code. While genetic mutations are a permanent, unchangeable process, epigenetics are not, they can be influenced; turned on and off.

So if many cases of recurrence are in fact not a recurrence at all, but actually a new eruption of cancer, the time immediately after treatment is vital. Critically, if offers the survivor a chance to influence the epigenetic environment. It is a chance to induce the recycling of damaged mitochondria, restore mitochondrial function, and stimulate the biogenesis of new mitochondria.

The first thing to do is remove any potential for mitochondrial damage. Incidentally, mitochondria are damaged by the same things that damage nuclear DNA; like carcinogens, radiation, and viruses. Avoid them. Eat clean food, drink pure water, and support your immune system to ward off viruses. Even a slight impairment of the immune system can have consequences. A recent study showed even moderate alcohol consumption increases the chance males will acquire an HVP infection independent of the number of sexual partners they’ve had.(7) HPV in men is responsible for multiple types of cancer including throat cancer. Michael Douglas’ high profile case of HPV-induced throat cancer sparked a surge of media attention about the disease experts now call an “epidemic among men”.(8) Healthy men and women can clear the HPV virus naturally, but even a modest impairment of immune function can cause an infection to linger, potentially leading to a chronically inflamed micro-environment and malignancy.

Next, the goal it to restore and enhance mitochondria function. It has been well established for decades that exercise stimulates mitochondrial biogenesis in skeletal muscle, but recent findings show that the same benefit extends to other tissues and organs throughout the body, including the brain.(9) Exercise has consistently been shown to not only reduce cancer risk, but to improve survival after diagnosis.(10)

Certain nutrients are known to increase mitochondrial efficiently and stimulate biogenesis. Rats fed diets supplemented with alpha-lipoic acid, acetyl-l-carnitine, biotin, nicotinamide, riboflavin, pyridoxine, CoQ10, resveratrol and taurine while subjected to exhaustive exercise showed greater mitochondrial efficiency and biogenesis compared to rats just subjected to exhaustive exercise alone.(11)

Caloric restriction (CR) is known to stimulate mitochondrial biogenesis. CR also induces a cellular process called autophagy. Autophagy is incredibly important. It is a highly refined process of “cleaning house”. Autophagy selectively removes cellular debris such as damaged proteins and mitochondria. If cancer is a disease of impaired mitochondria then one would expect CR to prevent both primary and recurrent cancer. A recent meta analysis of 44 studies showed there is an overwhelming consensus that CR prevents tumor initiation, slows progression, and attenuates metastasis.(12)

Oxaloacetate, an intermediate of the Krebs cycle, has been designated an “orphan drug” by the FDA. This nontoxic, natural compound has been shown to inhibit the growth of brain cancer by mimicking the molecular changes induced by CR. SCSC is currently funding a trial comparing oxaloacetate alone and in combination with a restricted ketogenic diet in a mouse model of highly-invasive, metastatic brain cancer.

A caloric restricted ketogenic diet (R-KD) has shown promise as a multifaceted cancer therapy. It’s strength being the way it uniquely prepares normal cells to tolerate toxic chemotherapy and radiation while simultaneously stressing malignant cells, making them selectively vulnerable to the same therapies. It appears to be especially powerful when combined with hyperbaric oxygen therapy (HBOT). The R-KD makes cancer cells selectively vulnerable to the oxidative pressure of HBOT. In a mouse model of metastatic brain cancer the two exhibited a beautiful, non-toxic synergy; a one-two punch to cancer cells.(13)

In one of the largest studies of its kind, a team of scientists analyzed cancer risk among 8,000 diabetics treated with metformin, a non-toxic, natural product of the French lilac plant. Over a 10-year period, they observed a 54% lower incidence of all cancers compared to the general population.(14) It’s not clear at all how metformin might prevent cancer on a genetic level. However, it is very clear how it might prevent cancer from a metabolic perspective. Metformin is a powerful activator of adenosine monophosphate-activated protein kinase or AMPK, a molecule activated by CR. All the same benefits of CR appear to be derived from taking metformin, including autophagy and mitochondrial biogenesis.(14)

The commonality between all of the therapeutic ways to enhance mitochondrial function and biogenesis highlighted above, is they are all nontoxic, restorative measures that not only target cancer initiation and progression, but can improve overall health and well being.

When the true nature of recurrence is combined with the evidence that cancer could be a disease caused by dysfunctional mitochondria, the cancer survivor is never taken out of the fight. There is no post-treatment purgatory where the survivors fate is determined by chance alone. Rather, it can be considered time of renewal. It is a chance to restore the mitochondria; to stimulate the removal of damaged ones and the growth of new ones — hopefully restoring the epigenetic environment and preventing recurrence.




13 thoughts on “Cancer Recurrence May Not be What You Think (what it really is and what can be done to prevent it)

    • Travis Christofferson Post author

      Hi James,

      Unfortunately, it is too early to tell for sure. A lot of evidence suggests it will, but until a good trial proves it, it is just speculation.

  1. Lou

    I thank you for writing Tripping Over the Truth and revealing the work of Drs Ko and Pedersen to a mass audience. I hope you’ll keep the world updated on any progress they make in bringing 3-bromopyruvate to market.

    Have you read Emanuel Revici’s text on cancer? He sees cancer as a failing of our immune system since cancer cells are found in healthy people frequently but they seldom become malignant and it’s difficult to graft tumors onto healthy animals; the tumor will seldom take unless the animal already has cancer.

    If Revici is correct, then the approach to treating cancer should be a killing agent such as 3-BP followed by a restoration of the immune system by restoring the balance between sterols and lipids.

  2. Neil caporaso

    Stimulating article. I disagree with one point. Yes, the genetics of tumors is quite complex, but finding tumors with zero mutations is a rarity that simply indicates there are still a substantial number we haven’t found or are tricky to detect in a given tissue sample. I do believe more work on understanding the metabolic contribution to cancer is a priority.

    • Travis Christofferson Post author

      Good point Neil. Finding samples with zero driving mutations is one inconsistency in the SMT. The classification of “driving” mutations is mostly based on statistics– the mutational frequency found across a groups of samples. Intuitively, it seems unlikely that there is a big contribution from infrequently mutated passenger mutations, but it can’t be entirely dismissed. I think it is the sum of the parts that leads one to a metabolic origin — the nuclear transfer experiments, the data from TCGA, the fact metabolic dysfunction permeates the spectrum of neoplasms, and more. Thanks for the thoughtful comment.

  3. Casey Moffett-Chaney

    I was following the KD (LCHF) when I was diagnosed with EPSSC localized in my left axillary lymph nodes in Sept. 2014. Chemo and radiation together were administered, and I continued to eat KD for the most part. In two months the cancer “melted,” to the delight and surprise of both my oncologists. I am still cancer free and eating LCHF.

    I am very interested in seeing cancer treated from the metabolic perspective and would like to know how I can help. I have been in contact with Dr. Ko, who asked me to facilitate an intriduction with Dr. Irfan Cicin at Trakya University in Turkey, who did a study on my particular kind if cancer because it was so rare and unique. Hopefully he may be interested enough to work with her.

    Thank you for writing Tripping Over the Truth.

  4. Nick K

    Seems to me that an important cancer distinction needs to be made that splits cancer into two groups. Group one is apparently random cancer growth and group two is cancer caused by a carcinogen (radiation, certain chemicals, viruses and the like).

    To me, random DNA mutation causing cancer defies nature. For starters there are mechanisms to prevent that. If random DNA mutations was the case, our evolutionary diversity would be much different. On the other hand, being bombarded by sufficient high energy particles causing DNA damage is a plausible explanation for a DNA cancer model. Similarly, ingesting cancer causing materials that affects the DNA resulting in cancer seems plausible. Likely carcinogens affect all aspects of the cell and cellular DNA, not just the nuclear DNA

  5. renee touriel

    thanks for this information…..what can I do as a breast cancer patient , stage 1 onco test low at 2 but high estrogen?I am on arimidix for 1 1/ years but had to stop because of trigger finger side effects…my oncologist had me try 2 other drugs but I couldnt tolerate tamoxifn and estremestese…….so I just got back on arimixed……..this is to prevent recurrence I was told……..this infor. on epigentics sounds better…..what should I tell my oncologist to do about it ?…..thank you……renee ^.^

  6. Lise McLain


    Has anyone read the book by Dr. Mark Sircus called “Sodium Bicarbonate” and it uses in
    cancer healing?

    I read it twice.

    Thank you!

    Lise from Maine

  7. sarah hodgson

    Hi very interesting information. I had bowel cancer aged 39, surgery and oral chemotherapy. Then was diagnosed with invasive triple negative breast cancer three years later… bilateral mastectomy followed by six months of chemotherapy. Generally I am in great health and never sick.. father died of lung ca aged 52, and mother pancreatic ca aged 69. My question has and still is can my cancers be justified as sporadic cancers at such a young age… If so what can I do to prevent reoccurrence other than stay healthy. . Regards sarah.

  8. Geoffrey Levens

    I have a bit of ADD so may have missed it but in article

    Cancer Recurrence May Not be What You Think (what it really is and what can be done to prevent it)

    I did not see any mention of chemo and radiation treatments often being carcinogenic in their own right and a cause of subsequent cancers post-treatment!

    Otherwise great post!


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