In a study conducted by a group of researchers led by Dr. Sanford D. Markowitz and recently published in the journal PNAS, the genetic changes that occur over time in colon cancer cells were examined
How long does it take from the moment a cell begins to undergo genetic changes until it becomes a cancer cell that forms a tumor and has the ability to send metastases? In a study conducted by a group of researchers led by Dr. Sanford D. Markowitz and recently published in the journal PNAS, the genetic changes that occur over time in colon cancer cells were examined.
A cancerous tumor is usually formed when, for various reasons, one cell begins to undergo a series of genetic changes (mutations), during which it acquires properties that allow it, among other things, to undergo increased divisions, lose its ability to function normally as part of the tissue to which it belongs, and acquire new abilities for migration and the formation of metastases in various tissues far from its initial location.
Colon cancer is among the most common cancers. The patients can be divided into two main groups according to the biological characteristics of the tumors. One group includes those that can be cured by surgical removal of the lesion. These patients usually do not develop metastases. The second group suffers from widespread disease, and they suffer from metastases mainly in the liver, despite the elimination of the primary tumor. This form of the disease is severe and fatal.
The purpose of the study was to model the rate of occurrence of the main events in the development of the cancer tumor. One of the main questions that interested the researchers was, at what stage does the cancer cell acquire the ability to create metastases?
For the purpose of the study, large sections of DNA from cells removed from the tumor and metastases were sequenced, and the genetic differences between them were examined. Surprisingly, it was found that in a large number of patients, the cancerous cells in the metastases were very similar in terms of the genetic changes found in them to the cells of the original tumor in the intestine. A finding that may indicate the existence of metastatic potential at a very early stage in the original tumor.
The researchers focused on the point genetic changes that appeared in the tumor and metastases (point mutations, random). These mutations appear randomly and at a more or less constant rate of one mutation every two years. Therefore, they can be a kind of molecular clock and a tool for estimating the time needed for the development of the tumor and the formation of metastases. From the findings of Dr. Markovich and his group, it takes about 17 years from a pre-cancerous polyp (adenoma) to an advanced cancerous stage (carcinoma). However, the time that passes until the moment the cancerous tumor begins to metastasize is very short, less than two years. Less than the time required for the appearance of new mutations. The time frame found with the help of the "molecular clock" corresponds to the known clinical findings in colon cancer patients.
From the findings of the study it appears that the features necessary for the formation of metastases are pre-existing in the original cancer tumor. Dr. Markovich and his group put forward two possible models that agree with this finding. According to one model, the cancer cells in the primary tumor cannot metastasize, but are close to that stage. Over time, a small population of cells within the tumor acquires mutations that give it the metastatic ability. This group of cells gives rise to metastases later in the progression of the disease. A second model suggests that all primary tumor cells have the ability to give rise to metastases, without the need for additional genetic changes.
According to the researchers, the ability to thoroughly sequence and characterize the genomes of cancer cells is an important tool for identifying genes involved in tumor development and understanding the key events throughout the progression of the disease.
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First of all thanks to Einav and Ami Bachar.
I was glad to see that the problem is troubling the medical establishment.
Although there were conclusions in the article that Einav referred to, that there is no danger in taking the biopsy, but unfortunately because of my professional English it was difficult for me to get an impression of how the conclusions were received.
I'm afraid that the conclusion is only within the framework of statistical measurement error so I'm definitely not calm. I also did not understand if they operated in two groups, one without a biopsy and one with, and only then came to conclusions. I am afraid that the approach is still an unwarranted comforting approach.
The approach of Einav, who tries to reassure with her words: "A cancer cell that is capable of metastasizing does not "need" to wait for the biopsy needle to release it", is not acceptable to me. There is no reason to help him undress.
Anyway, I thank you both again for your response.
Have a good and healthy weekend
Sabdarmish Yehuda
Hello Sabdarmish,
My mother, who will be distinguished for a long and good life, was similarly fortunate, only that in her case - as well as in other cases I know of - the procedure is such that in advance of the biopsy, at the same time as the dissection, there is also an examination for the presence of cancer and at that point they decide how to act.
As you know, I do not practice medicine and my knowledge in this field is very limited. I don't know freezing and removing techniques, but it is clear to me that the technique is limited, because freezing a cell means killing it. Of course, when it comes to areas of "less important" or at least regenerating tissue, such procedures may be possible.
During my university days, I once heard a lecture by a man who, if I remember correctly, also won a Nobel Prize for this matter: he talked about angiogens, which are (again, to the best of my memory) substances that cause blood vessels to form. When a cancerous lump forms, it needs to eat and therefore causes the creation of blood vessels around it, which will feed it with oxygen and flow energy to it. That person thought in his heart that measuring the amount of angiogens in the blood, could indicate the inventions or the beginning of cancer. Angiogens are found in the blood circulation for example in cases of injury or amputation.
Indeed, it turned out that the method works and is even much more sensitive than mammography, which requires a minimum size of a cancerous lump that can be seen (a few mm). The angiogens running around in the blood know how to detect a small, even invisible, cancerous lump that is already beginning to require the body to build a food and supply network around it.
I assume that when a cancerous lump is still in its infancy, it is difficult to detect it, so to stay on the safe side, you have to do periodic tests that cost a lot of money to the health insurance funds or to the tax payer if the test is in the basket of tests. The next cheapest thing is to wait for the lump and test it in seemingly safe ways that try to minimize the drift of cells into the bloodstream. Also, Einav's reaction is enlightening regarding the ability of cancer cells to metastasize in this way.
to my people
If so, are different methods used to prevent dispersion?
What do you think, for example, about freezing a place for taking the biopsy so that the scattering of cancer cells does not happen. And in general, isn't it better to avoid a biopsy and decide only based on other data even if they are not absolute.
I think this is still not taken seriously. I asked my late mother to avoid the biopsy and to treat the lump in the breast as a cancerous lump. The doctors refused and were only willing to promise that they would do it quickly.
Why does this remind me of the maternity fever of a hundred and fifty years ago. I have a fear that the doctors are causing the spread of cancer and metastases with their own hands, and will not be willing to admit it, just like 150 years ago.
I appreciate you, Ami Bachar, as a very serious and responsible person. Nevertheless, your answer is reassuring without any justification.
Quote: "If it is indeed cancerous, the surgery will do it anyway so that the biopsy can be considered part of the surgery" end of quote.
What does "anyway part of the surgery" mean? Is part of the surgery to penetrate the cancerous mass, tear it apart and scatter cancer cells into the bloodstream?? Is this part of the surgery? The entire mass must be removed without scattering any cells into the bloodstream.
I wonder if anyone would be willing to take up the gauntlet on this issue.
Have a good evening
Sabdarmish Yehuda
Hello Sabdarmish,
Everything you said is true.
Oh, what what?
If the biopsy does reveal that it is cancer,
Even if it is something that is removed in surgery anyway
Today it is accepted in any case to perform chemotherapy.
Both the biopsy and the surgery for removal are a problem for the reason you mentioned.
If it's not cancerous, no problem.
If it is, the surgery will do it anyway so the biopsy can count as part of the surgery. Dispersion of cancer cells in the bloodstream is taken into account and treated with the various methods.
Greetings friends,
Ami Bachar, Sde Booker
Yehuda Shalom,
There are debates in the literature regarding the risk of taking a biopsy.
It is known that sometimes after an invasive intervention you can find signs of the tumor cells in the bloodstream (for example - http://www3.interscience.wiley.com/cgi-bin/abstract/106596236/ABSTRACT), but it is not entirely clear whether they can form new tumors.
In 2004, an article was published that examined over 2000 women who underwent a biopsy due to breast cancer and showed that there is no increase in risk following the biopsy (http://www.nature.com/bjc/journal/v91/n10/full/6602205a.html#abstract).
Not every cancer cell is able to metastasize. And usually the immune system knows how to identify and eliminate cells outside of their natural tissue. In addition, even the cancer cells themselves do not always have the tools to survive without their supportive environment. And in short, in my opinion, a cancer cell that is capable of metastasizing does not "need" to wait for the biopsy needle to release it...
Have a good evening 🙂
This article proves the great importance of early diagnosis.
It would be desirable if they said a few words on this topic as well.
Another thing that always worries me is:- Is there any danger in the act of taking the biopsy for the purpose of the initial diagnosis. The very fact that you penetrate the suspicious lump and cut a part of it can already cause a significant amount of cancer cells to be scattered into the bloodstream. Have studies been done on this topic?
Have a good day
Sabdarmish Yehuda