What is the root cause of cancer

[wolram]

One reads of cancer ever more these days, it seems like one can get cancer of anything, surly there must be a different switch to switch on breast cancer or prostate cancer.

 

[Borg]

The prevailing belief used to be that each cancer was thought to due to mutations related to that organ. However, there wasn't any single treatment that ever had much success for any given type of cancer. In the last few years, doctors have discovered that the drugs that seemed to have limited success, have very good success against specific mutations regardless of the organ in question. Now instead of trying to develop a breast cancer or lung cancer drug, they test drugs based on the genetic mutation.

 

[1oldman2]

One reads of cancer ever more these days, it seems like one can get cancer of anything, surly there must be a different switch to switch on breast cancer or prostate cancer.

Until I was nearly 20 years old I had never met anyone with cancer, at this point I have lost count of friends and family who have died of it. My wife and I both grew up in a town named Libby Montana Which is famous for two things, Great trout fishing and the home of Mesothelioma. This probably explains the increase in cancer cases I have noted. While WR Graces Zonalite operations definitely affected (and ended) a lot of lives, it seems to me that everyday life is loaded with triggers just waiting for the right conditions and genetics to come together. All the variables make avoiding cancer similar to shooting dice, the best a person can do is try and keep the odds in your favor by making smart lifestyle choices.

 

[Hornbein]

One reads of cancer ever more these days, it seems like one can get cancer of anything, surly there must be a different switch to switch on breast cancer or prostate cancer.

There are many causes. Mutagens, ionizing radiation, viruses, genetics...

 

[Asteropaeus]

The difficulty of having an organism with differentiated tissue. Once that control mechanism fails, those cells that don't obey the rule have an advantage and out-compete those that do follow the differentiation rules.

 

[Choppy]

Cancer incidence is increasing. If I recall I think current predictions are for increases of roughly 4% per year world wide, and less for the developed countries.

One of the reasons for this is that people are living longer. Cancer has surpassed heart disease as the number one killer of people under 85, but I believe this is because we're getting better at treating heart disease. And the mean age of the population is increase. All of this translates to more cancer because the older you get, the higher the probability is that you'll develop cancer - regardless of lifestyle choices. You can still lower your risk by making good lifestyle choices, but even for the healthiest lifestyles, the probability increases with age. See: What Causes Cancer: Bad Luck or Bad Lifestyles?

So in a way, the root cause of cancer is: living.

 

[Ygggdrasil]

The underlying causes of most cancers are mutations that either activate proto-oncogenes, genes that lead to uncontrolled cell growth and division, and/or inactivate tumor suppressor genes, genes that protect against uncontrolled cell growth and division. These mutations can come from a number of different sources: they can be inherited from one's parents, they can come about due to exposure to mutagens and carcinogens in the environment, or they can arise during the normal course of cell division (see the Insight article that Choppy linked to).

Of course, cancer is not one single disease but rather a collection of related diseases. Cancers from different parts of the body are often very different from each other both in how the disease manifests itself and in the specific mutations that drive the disease. Sometimes, cancers of the same body type can be very different between individuals (cancer cells within the same individual can also be quite different from each other). For example, there are many different subtypes of breast cancer, some of which can be distinguished based on the types of receptor molecules present on the cancer cells. The classification of the tumor greatly affects the treatment and prognosis of the disease. Childhood cancers in a particular organ often are associated with different mutations than adult-onset cases of cancer in the same tissue.

Some mutations are linked to a number of different cancer types occurring in different parts of the body. Examples include mutations to telomerase, p53, or the BAF complex. Other mutations, however, are associated with very specific cancers, such as the BRCA mutation that increase the risk of breast and ovarian cancer. Interestingly, the BRCA1 and BRCA2 genes (mutated in individuals with BRCA mutations) are tumor suppressor genes that encode proteins involved in DNA repair. These proteins and their associated repair processes occur in all cells and are important throughout the body, and we don't really understand why these mutations specifically lead to breast and ovarian cancer.

 

[WWGD]

So in a way, the root cause of cancer is: living.

Living is the leading cause of death: 100% fatality rate so far.

 

[phyzguy]

Cancer incidence is increasing.

While this is the general perception, I don't think it is true. If you look at these two files from the American Cancer Society, you will see that cancer Death Rates are trending strongly downward as treatments improve, and that Incidence Rates are also trending downward, albeit more slowly. Here is a link if you want to explore more:

https://cancerstatisticscenter.cancer.org/#/data-analysis/

 

[Choppy]

While this is the general perception, I don't think it is true. If you look at these two files from the American Cancer Society, you will see that cancer Death Rates are trending strongly downward as treatments improve, and that Incidence Rates are also trending downward, albeit more slowly. Here is a link if you want to explore more:

https://cancerstatisticscenter.cancer.org/#/data-analysis/

I'll double check my numbers when I have a chance. I suspect the difference is either yours are age-adjusted or mine are absolute.

 

[jim mcnamara]

@Choppy His data appears to be age-adjusted. Also note - as a cohort ages the rate of cancer occurrence increases within that cohort -
Cancer has been around for a while - like 70+ million years - here is a non-technical discussion, which
links to a more technical paper at nature.com.

Oooops: need to add the link

https://www.theguardian.com/science/2003/oct/23/dinosaurs.science

 

[Laroxe]

If you consider that every cell in our body contains all our genetic information when cells divide there are a great many mechanisms in place that are needed to control the process, we don't understand how it all comes together but we are identifying more parts of the process. The vast number of genes that have to be controlled, either switched on or off is controlled by other elements inside and outside of the cell, the cells surface is covered with receptors that pick up information to help in this control. This means there are lots of genes that may be involved, in different combinations and lots of ways in which these genes can go wrong, even when the cancer develops the genetic changes seem to accumulate as the tissues become more unusual. One of the things effecting incidence is when we identify things that greatly increase risk, smoking being the most significant and as that becomes less fashionable it has an overall effect on incidence, but finding something else in our lifestyle that will have such a big effect is unlikely. As Borg suggests there is a major effort to understand these mechanisms and produce drugs that specifically target receptors that control cell proliferation, hormones are one group but there are more and more drugs becoming available, I've just been reading about GABA receptors on cells being a new target. In the west we are already achieving a cure rate in excess of 50% overall and we are just at the start on this new medical revolution.

 

[mjs]

Targeting specific molecular pathways has been proven a difficult issue, due to the complexity of molecular cross-talks, which enables cancer cells to escape treatment. Immunotherapy (checkpoint inhibitors and adoptive immunotherapy) is currently the most promising area and most research nowadays focus on it.

As per the OP's question:
Apart from cancer-generating mutations, interactions between cancer cells and its surrounding stroma play a key (and yet not fully understood) role. Additionally, the ability of cancer cells to avoid recognition and destruction by immune cells is another key factor...In conclusion, cancer cells avoid regulation and they reach a state that, given their properties they gain, i would describe as "bad embryology"...

 

[christopher.s]

I would say that the "root" cause of cancer is metabolic dysfunction. I think focusing on the genes can cause one to lose sight of what actually constitutes a "healthy" cell vs. one that is damaged. For instance, if you look at levels of LDH (lactate dehydrogenase, which is an enzyme that catalyzes the conversion of a metabolic waste product, lactic acid) in cancerous cells, you will without exception find they are elevated. In addition, drugs that target metabolic pathways in particular (aspirin, methylene blue, etc.,) actually show great success with treating cancer. Search on pubmed for analysis of aspirin and cancer, and you will find that risks of nearly all kinds of cancer can be reduced by it.

This brings us to the topic of cellular coherence. Cells by themselves are primitive, it takes a lot of regulation (hormones, etc.,) to have them work together in a complicated organism such as a human. The cells in the complex organism are actually part of a coherent field, which has to do with the water structuring and energetic state of the cell. Disruptions in this field will cause the cell to revert back to primitive metabolism, which is glycolysis. You will find that cancer cells are almost exclusively operating in this "fermentation" mode of energy production. This is not an efficient process, and leads to lots of metabolic waste, which disrupts cellular coherence.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2849637/

 

[Ygggdrasil]

Metabolic dysfunction is certainly involved in cancer and the Warburg effect—that cancer cells seem to rely on glycolysis rather than oxidative phosphorylation for ATP generation—is definitely true. It is hypothesized (for example, by the Science paper you cite) that the Warburg effect comes about because oxidizing glucose all of the way to CO₂ prevents the cell from incorporating the carbon in the glucose into cellular building blocks. Therefore, by preventing oxidative phosphorylation and only oxidizing glucose to pyruvate, an important metabolic building block, the Warburg effect allows the cell to extract energy from glucose while still retaining the carbon from the glucose to use as biomass for building new cells.

Your interpretation that cells are part of a coherent field is not discussed in that paper and does not sound correct to me. Certainly, intercellular communication and regulation are important, but these are mediated by intercellular contacts and signalling molecules, not through the water structuring. Furthermore, although some cancer treatments do target metabolic pathways, I am not aware of any evidence showing great success with treating cancer with aspirin and methylene blue.

 

[DrDu]

The prevailing belief used to be that each cancer was thought to due to mutations related to that organ. However, there wasn't any single treatment that ever had much success for any given type of cancer.

That's not completely true and there are success stories. For example for chronic myeloic leukaemia, which was the first cancer for which the molecular mechanism was understood, there is specific medication, namely tyrosine kinase inhibitors, which, although they have to be taken lifelong, almost cure the disease.
There is even a popular book on this fascinating story:
The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level, by Jessica Wapner

 

[Borg]

That's not completely true and there are success stories. For example for chronic myeloic leukaemia, which was the first cancer for which the molecular mechanism was understood, there is specific medication, namely tyrosine kinase inhibitors, which, although they have to be taken lifelong, almost cure the disease.
There is even a popular book on this fascinating story:
The Philadelphia Chromosome: A Mutant Gene and the Quest to Cure Cancer at the Genetic Level, by Jessica Wapner

I wasn't aware of that. Thanks.

 

[mjs]

I would say that the "root" cause of cancer is metabolic dysfunction. I think focusing on the genes can cause one to lose sight of what actually constitutes a "healthy" cell vs. one that is damaged. For instance, if you look at levels of LDH (lactate dehydrogenase, which is an enzyme that catalyzes the conversion of a metabolic waste product, lactic acid) in cancerous cells, you will without exception find they are elevated. In addition, drugs that target metabolic pathways in particular (aspirin, methylene blue, etc.,) actually show great success with treating cancer.

In chronic myelogenous leukemia, targeting the specific mutation k-kit actually cures the disease. Why?
LDH is not always elevated in cancer. It is a product of cell destruction and its elevation indicates high tumor burden and advanced disease...
As far as i know, there are no cancer treatments based on methylene blue or aspirin. Maybe aspirin has a minor preventive role but its most likely attributed to its anti-inflammatory effects, that reduces the rate of novel mutations...

I wasn't aware of that. Thanks.

Glivec is effective in treating CML by acting to the product of c-kit mutation, but
a)this is the only example of curative treatment that we have by targeting mutations, despite many efforts and extensive research, and despite the existence of second generation sequencing that dramatically improved our knowledge regarding cancerous driver mutations.
b)Targeting c-kit is not organ specific, as this strategy is quite effective in other diseases as well, such as GIST's, although the results are not so impressive as in the case of CML.

 

[Laroxe]

I don't think any of these ideas contradict the underpinning idea that it is genetic mutations that drive cancers, it is gene expression that controls all of these processes and that code for the various types of growth regulating receptors. In many ways this explains the many varied types and behaviours in cancers, there may be certain required changes to make cells cancerous but then there are a huge number of changes that can effect all sorts of cellular processes.
This doesn't change the fact that targeting various metabolic pathways and receptors are the main tools we use, its often easier to target gene products than attempting to modify the genetic structure when it can be so variable, even within the same tumour. I think the problem is in trying to understand these things as a linear process, from gene's to their effect, when really at every point there are multiple things controlling how these genes are expressed. Remember that a fault in any single metabolic pathway would not be sufficient to constitute cancer, a faulty cell would simply be killed by the immune system. Its also wrong to consider the role of certain drugs as not particularly useful, for cancers that use signalling from sex hormones in controlling division their use has revolutionised outcomes.
I believe the main uses for Aspirin is in preventing some cancers rather than treatment and its suggested this might be due to its anti-inflammatory effect, chronic inflammation being associated with increased DNA damage. Methylene blue does apparently alter certain metabolic processes but the only people using it as a treatment for cancer are alternative therapists. It is used in surgery as an indicator and as a photo-sensitiser in laser surgery, this in fact suggests it didn't fulfil its potential. It is also thought to be potentially carcinogenic itself.
http://cancerres.aacrjournals.org/content/amjcancer/24/1/80.short
One thing we all seem to agree on is the need for a greater understanding of all these processes.

 

[DrDu]

The problem with cancer is that the mutations that cause it make the genome of the cancer cells instable. Hence the cancer cells mutate further and in the course of progression loose more and more of the distinguishing features the original cells had. Often, some therapy is initially successful, but it fails to kill the most mutated cancer cells, which then lead to a recession.