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The Cancer Cells That Leave Home Have Extra DNA Capabilities

by George L Gabor Miklos PhD and Phillip John Baird MD PhD

The cells that leave the primary tumor have different DNA characteristics to those that remain. It is their altered properties that enable these emigrants to leave in the first place and for their descendants to infiltrate and destroy vital organs. (20, 21, 22, 30, 31)

Normal cells

All normal cells have two copies of their DNA, one set from the mother and one set from the father. There are thus two DNA code books (instructions-for-cell-survival) in every normal cell. If one book is damaged, there is always a good copy from which to make repairs in an emergency. Normal cells carefully follow the instructions encoded in their DNA and execute them in a particular order and at specified times. Normal cells are tightly constrained by their two-book genetic operating manuals.

Cancer cells

By contrast, cancer cells that have left the primary tumor and are in transit or have arrived at their final destinations, have massively disrupted DNA contents. Their instructions-for-cell-survival books have been copied and they have more than two of them, but with profound differences. Enormous errors have occurred during the copying process so their books now contain some extra chapters, sentences and paragraphs, while some other chapters, paragraphs and sentences have been completely deleted. Furthermore, differing amounts of text have been shifted from one place to another and at the most basic level, single letters have been changed. These single letter changes are commonly referred to as mutations (6,32).

The extent of these massive alterations in DNA is aptly described by Dr Garth Anderson, of the Roswell Park Cancer Institute in Buffalo, NY; "in most adult solid tumors the genome is shot to hell by the time the tumor is found..." and ...a mutation will not be in every cell in the tumor." (33)

The danger lies in the diversity within a cancer cell population

The mistake-prone process of DNA copying, cutting and pasting that goes on in cancer cells produces remarkable outcomes. Cancer cells no longer have to obey instructions. They have been liberated from the rigidity of conventional two-book genetic operating manuals. The ongoing process of massive alterations in DNA provides a cancer cell population with novel instructions on how to cope with various emergencies. Thus when chemotherapeutic drugs are encountered, some cancer cells in the population have different ways of dealing with drugs. No matter what defenses the body may deploy, some cancer cells in a population always have a new combination of instructions ready to face a crisis.

The cancer cells that leave home have increased informational diversity

The cancer cells that leave a primary tumor are often first found in the nearest lymph node draining the tumor and later in more distant places such as the bone marrow. A comparison of the DNA contents of individual cancer cells from the lymph nodes and bone marrow of the same patient to those of individual cells in the primary tumor reveals that cancer cells at these different locations have accumulated their own specific changes in their DNA contents. (22)

The cancer cells that leave the primary tumor represent a diverse population upon which selection will act. Some cancer cells are destroyed by the immune system, others reach the lymph nodes and progress no further, whereas still others reach an organ but are held in check by the local resident cell population and cannot proliferate. Finally, some cancer cells survive all these hazards, grow at their new sites and ultimately destroy a vital organ. In a nutshell, this is metastatic cancer.

Most cells in a primary tumor never leave

Only a small number of the cells in a primary tumor ever develop the DNA alterations to emigrate (21,34,35). If all cells had the capacity to leave, no primary tumor would be left (21). When the cells of a primary tumor are tested both clinically and experimentally for their ability to form a new tumor, only approximately 1 in 50,000 cells has the capacity to do so (34-38). Only cells that have sufficiently altered genetic operating systems or stem cell-like properties (39-41) break free of the local constraints and depart. Normal cells always remain in their local neighborhood.

(Next up: Drug Resistance and the Return of Cancer, and, New Frontier or Yet Another Unfulfilled Promise?--Dean)

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Jack G (mail) (www):

The mistake-prone process of DNA copying, cutting and pasting that goes on in cancer cells produces remarkable outcomes. Cancer cells no longer have to obey instructions. They have been liberated from the rigidity of conventional two-book genetic operating manuals. The ongoing process of massive alterations in DNA provides a cancer cell population with novel instructions on how to cope with various emergencies. Thus when chemotherapeutic drugs are encountered, some cancer cells in the population have different ways of dealing with drugs. No matter what defenses the body may deploy, some cancer cells in a population always have a new combination of instructions ready to face a crisis.



It's no mistaken process, it is an adaptational process. It only seems mistaken when compared, relatively speaking, to "normal cells."

Cancer cells, although I would not express it exactly in the manner described above are indeed far more flexible, adaptive, and capable than normal cells. They replicate without the normal degenerative processes of cellular necrosis.

Therefore if one tamed and domesticated the seeming wildness of cancer (in comparison to normal cells) while augmenting the adaptational advantages offered by cancer, then cancer would be the key to both potent increases in longevity and immense rewards concerning immune capabilities and cellular injury recovery.

The real trick is in taming and regulating cancer, then exploiting the multiple benefits it provides, due to it's very nature.

Cancer is the Trojan Horse of cellular disorder, but waiting within it is an army of immense beneficial capability if properly exploited and used to advantage. It is no accident cancer is what it is, functions as it does, and acts as it acts. It's a clue. A clue from nature and God.

But first you have to shift your psychological paradigm from the idea that Cancer is always death and the enemy, to see that Cancer is really Extended and more Adaptive Life waiting to happen.

If used the way it can and should be used.
8.1.2007 12:29pm
TallDave (mail) (www):
Jack,

Yeah good point, the mini-Darwinism cancer exhibits can probably be harnessed eventually.

The human genome is a crappy mess, a bunch of self-perpetuating accidents that just happen to give rise to intelligence. We'll probably have to rewrite much of it.

This seems relevant.

Science Daily — Killing cancerous tumors isn't easy, as anyone who has suffered through chemotherapy can attest. But a new study in mice shows that switching off a single malfunctioning gene can halt the limitless division of tumor cells and turn them back to the path of their own planned obsolescence.
8.1.2007 4:27pm
Hank Barnes (mail) (www):
Jack G,

Interesting observations. But I differ, respectfully, with one central proposition you make:

It's no mistaken process, it is an adaptational process. It only seems mistaken when compared, relatively speaking, to "normal cells."

A tumor on your lung is not "adaptational." The billions of cells that comprise your lung and respiratory system are, by way of analogy, an highly tuned orchestra, with a specific function, ie to play Beethoven's Fifth in perfect harmony. That is the function.

In contrast, a cancer cell loses all function. Its mutant DNA produces mutant proteins, leading to mutant tissues. It is the opposite of "adaptational." It doesn't help the orchestra play a better or different version of Beethoven's Fifth -- it starts randomly thrashing on the violin, making discordant noise, that, if not arrested, and spreads, will wreck the entire ensemble.

My thoughts.

Barnes
8.1.2007 5:40pm
Ronald Coleman (mail) (www):
Yes, as Hank said -- everyone was panicking about Ebola a few years ago. Then we realized than an infection that almost instantly kills its host quickly and violently isn't really built for a brilliant career.
8.1.2007 6:03pm
McKiernan:
Then again, it could be that the cancer cell is looking for a function or maybe just an orchestra leader.
8.1.2007 6:30pm
TallDave (mail) (www):
Hank,

No, I think Jack's right. At first I wanted to disagree too, on the basis they are giving up their natural function, but really what we're seeing in cancer is the birth of a new combination of genes, followed by the inevitable Darwinian processes that dictate that the most successful gene combinations survive.

Like all life, the new geneset's only real "function" is to survive and replicate. Unfortunately for both them and the host, they usually kill the host, which ends badly for everyone. But since there's only one host, cancers never learn better.
8.1.2007 7:03pm
Hank Barnes (mail) (www):
Then again, it could be that the cancer cell is looking for a function or maybe just an orchestra leader

The only function of a cancer cell is to replicate. A tumor on your hand never adapts into a 6th finger.

In contrast, a liver cell has 2 functions -- (1)it is part of a system to filter harmful substances from the blood and (2) it replicates to sustain the system.

A cancerous liver cell loses function (1), leaving only function (2).

A tumor is like a politician, who never votes, never attends committee hearings, but devotes 100% of his time to fundraising for next election. A perpetual do-nothing machine.


Hank
8.1.2007 7:10pm
Jack G (mail) (www):

It's no mistaken process, it is an adaptational process. It only seems mistaken when compared, relatively speaking, to "normal cells."



A tumor on your lung is not "adaptational." The billions of cells that comprise your lung and respiratory system are, by way of analogy, an highly tuned orchestra, with a specific function, ie to play Beethoven's Fifth in perfect harmony. That is the function.

In contrast, a cancer cell loses all function. Its mutant DNA produces mutant proteins, leading to mutant tissues. It is the opposite of "adaptational." It doesn't help the orchestra play a better or different version of Beethoven's Fifth -- it starts randomly thrashing on the violin, making discordant noise, that, if not arrested, and spreads, will wreck the entire ensemble.



I wasn't speaking about it's relationship to normal cells. Or it's function as currently construed in relation to how it functions vis-a-vis normal cells.

Let me put it to you this way.

Cancer cells are super cells in a sense. When put against "normal cells" then normal cells, over time, stand little chance in prevailing in a given environment (say an organ, and assuming enough cancer cells can gain access to enough resources) because cancer cells function in a superior manner, even down to competition for resources.

The environment of the organ (the organic system in which either normal cells or cancer cells live and reproduce) is constructed primarily of normal cells and the parameters regarding their requirements. As you say, the lung is synchronized for their functioning methodology and system of reproduction and perpetuation.

A cancer cell is a danger precisely because it is superior. If you interjected a lion into a den of housecats then the housecats are at a disadvantage and the home they have constructed stands little chance of survival. Because the body is a closed system eventually the lion eats everything and starves too. But it is still vastly superior in most ways. This doesn't mean cancer can't or won't kill of course - when running wild it can kill much more effectively than normal cells. But that also makes it better at survival in most any given environment or situation.

I'm no 19th century Darwinian who thinks survival is an excuse for any pursuit.

I'm not saying let cancer cells thrive in place of normal cells.

I'm saying let cancer cells be tamed and eventually let those tamed cancer cells replace normal tissue, in a certain manner of speaking. I'm saying when something is good at something, like survival and adaptation then there is a reason for that. Learn from it, exploit it, make it your own. I'm saying normal cells are not so great either, they are just normal. Mediocre, programmed to self-necrosis. They are normal only in the sense that they are what we are used to. They are normal because they are us, they are not superior or better than cancer. They are normal in the purely staististical and mundane sense.

If every cell in a creature's body were composed of domesticated cancer cells, (not wild cancer cells, to distinguish the matter - they are wild by the way only in comparison to normal cells) and those cells functioned to exploit the benefits afforded by cancer cells then every organ would likewise be attuned to function with the requirements of domesticated cancer cells. The aging of the organism would practically cease, immune system functions and adaptability would be greatly enhanced, injury recovery improved, precisely because of what cancer can do.

But it is not cancer versus normal cell. It is taking the benign and yet limited functions of normal cells and enhancing those with the positive and fluidly adaptive attributes of cancer cells and then taking cancer cells and taming their more destructive elements and creating a new kind of cell which is a type of hybrid to replace both.

But you can't simply look at cancer as the Monster of Death for in truth it is the Master of Life. It is so good at living as a matter of fact that unless attacked piously and sometimes in a very sustained manner it will over time overwhelm normal cells who are pre-programmed to self-destruction. Who are by comparison weak and inefficient.

You can't just let cancer run wild, but assuming it must be eliminated instead of tamed and exploited is to miss the potential of what it really represents.

An opportunity, not at necessary death but a biological and genetic tool to achieve longevity and physical, genetic, and immunological flexibility.

It should be taken, reformed, reprogrammed, domesticated, and exploited.

It could help produce a hybrid type of human (or animal for that matter) cell which would play it's own music.

A superior orchestra for a superior organism. (Not in the mol sense of course, but in the physical sense).

The real aim of cancer research in my opinion should be how to use cancer properly, to exploit it for benefit just as tamed and domesticated antibodies (which are pathogenic to other organisms) are used to assist the immune system of humans and animals.

Suppose for example that earlier in our history medical science and researchers had decided that every pathogen needed to be wiped out instead of exploited beneficially? Suppose it were even possible?

Vaccines would not be possible. The aim would be to kill any and all pathogens instead of exploiting them. You need a pathogen to create a vaccine to enhance the immune system when the immune system if weak or inexperienced.

Then when, as would certainly happen, a new pathogenic organism eventually arose our immune systems would be so atrophied through lack of contact with danger (because the aim of medicine had been to eliminate all pathogens rather than tame them) any small infection would obliterate entire populations.

Everything that exists in life does so for a purpose, even if it is not functioning optimally. Everything can also be exploited if properly approached. Then turned to advantage, but you have to get over the idea that it must at all costs be annihilated in an unquestioning and uncritically unscientific fashion.

I'm proposing that it is not the job of medical science, or genetic researchers, to assume that every pathogen, danger, disease, disorder, or malfunction deserves automatic annihilation. That destruction automatically leads to better immunological security, longevity, or biological functioning. Wipe out all danger and in the long run you do harm as a physician because when danger reappears, as it always will, then you are weak, vapid, helpless, and infirm. To do no harm sometimes means to conquer and exploit, not kill and annihilate. Superior and improving men, creatures, and beings become stronger by absorbing the advantages of their opponents and environments and using those advantages to a beneficial end. The same is true of certain pathogens and even disorders.

To me cancer is just another one of those innumerable clues left by God and implanted in nature that could be beneficially exploited if man viewed cancer for what it can really and eventually accomplish, rather than for what it immediately seems to achieve.

I hope that explains better what I was driving at.
8.1.2007 7:20pm
Jack G (mail) (www):
I just thought of a better way to say what I meant without an ass load of words.

It is simply a current and present paradigm of medicine, genetics, and science to assume that cancer is nothing more than a danger and that by comparison normal cells are to be in every way preferred.

It is not an Eternal Truth, merely a modern paradigm, a theory, a construct, an assumption. A basically untested one at that.


Something most people automatically assume because it is normal to do so. Or because they've never struck out at the problem from reverse.

But it is no more necessarily true a proposition than the idea that "normal cells" are "normal."
8.1.2007 7:29pm
Dean Esmay:
I don't think it likely that "taming" cancer cells is going to happen. Their defining trait appears to be the absolute chaos of their DNA replication. They do indeed appear to be much like a new species (or "mini-species") but how can you get regulated function out of the chaos that is the replication process that appears to be what really defines them?
8.2.2007 4:48am
Jack G (mail) (www):

but how can you get regulated function out of the chaos that is the replication process that appears to be what really defines them?



By creating a genetic chimera between cancer cells and normal cells.
8.2.2007 6:13am
Jack G (mail) (www):
I should more accurately respond with greater detail.
My first reply didn't say a lot.

As to the exact method of creating such a chimera and such a successfully functioning structure, that would have to be achieved through trial and error, as with any experimental biogenetic process.

Just as currently all efforts are bent through trial and error at creating cancer "cures." The paradigm of which is either the destruction of cancer or the reversal of tumorous cancer material to a state of "normalcy."

What I am suggesting is not a return to normalcy, nor the destruction of cancer per se, but it's replacement. Rather it would be the creation of a multi-capacity chimera with modified operational regulatory and replication processes. You would not eliminate the cancer cell's ability to mutate and modify itself to advantage, rather you would regulate it in an advantageous and controlled manner.
The chimera would be the "cure." (Or one possible cure, there are other ways this could be done but a chimera seems to me to offer the greatest set of possible advantages.)

A chimera that could compete with and replace cancer cells, and if successful enough over time, eventually replace the normal cells of the entire organism for enhanced biological functioning (in several different ways) and increased longevity.
8.2.2007 6:33am
Jack G (mail) (www):
You would not eliminate the cancer cell's ability to mutate and modify itself to advantage, rather you would regulate it in an advantageous and controlled manner in relation to the entire organism and/or affected organ, not just in relation to itself.



I didn't express that very thoroughly or clearly, so I restated it.
8.2.2007 6:42am
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