Cancer - not what you thought

New studies indicate a genetic link between different types of violent tumors

Cancer is a disease characterized by a very rapid proliferation of cells, which the body has lost control over the rate of their division. In fact, it is not a single disease, but a long series of diseases that ultimately have one central characteristic - the uncontrolled division of cells. What is it similar to? As if we treated all headaches as one disease, even though a headache is a symptom of many diseases and different medical conditions. So it is true, the cancerous tumor is not only a symptom, but it is also not exactly the cause of the disease. The tumor is the phenomenon we see, the result of genetic changes occurring in the body's cells.

The accepted classification of the types of cancer is done according to the organ or tissue they attack. Most of us say "breast cancer", "lung cancer", "liver cancer", etc. Doctors also largely use this division, although they also have many other diagnoses related to the type of cancer cells (such as carcinoma, sarcoma, lymphoma, etc.), the stage of development of the tumor and its pattern of development. There are "violent" tumors that develop quickly and cause severe damage to tissues and organs, and there are tumors that develop very slowly and are hardly noticeable. Two studies that have come to light in recent days strengthen the possibility that the existing method for classifying cancerous tumors is not appropriate, and that the tumors should be classified according to genetic characteristics, regardless (almost) of the organ they attack.

How does cancer form?

The key to cancer processes are mutations - that is, mistakes in the DNA sequence. The genetic code of all of us consists of a total of four different letters, which are actually chemical bases, marked for convenience with the letters A, G, C, T. We still do not understand the function of most DNA sequences, but we know very well that one of their central functions He carries the instructions for the production of proteins. All three "letters" in the DNA sequence are a code for one amino acid, while a complete protein is a chain consisting of hundreds and even thousands of such acids. After the production of the chain, the protein organizes into a perfect spatial structure. A mistake in the DNA sequence may be completely meaningless. It is possible that it will not cause a change in the protein sequence at all, or will cause only a minimal change, which will not affect the structure of the complete protein or its function. On the other hand, a critical mistake in a critical place in the sequence of the amino acids, may lead to a defect in the structure of the entire protein, and possibly even cause the entire protein to not function. Such mutations are indeed very rare, but when each cell in our body contains about three billion such letters, they can certainly occur, despite the sophisticated control mechanism that should prevent most mistakes. Most researchers believe that the development of a cancerous tumor is the result of the accumulation of mutations. That is, several critical mistakes in the structures of some proteins, or important DNA sequences, are needed to bring about the same terrible situation of loss of control over cell division. Unfortunately, our knowledge of the mutations that cause cancer is still very poor. Ultimately, the accumulation of mutations in the structure of proteins, or in control sequences (sequences of DNA that mark where the gene begins and ends), damages one or more of the mechanisms that are supposed to monitor cell division. It is also possible that the injury is one of the security mechanisms - for example, cells have a "self-destruction" mechanism, which is supposed to operate if the cell deviates from its normal function, but in certain types of cancer this mechanism does not work.
Scientists today know quite a few mutations that are associated with different types of cancer, but knowledge about their direct relationship to the disease, about the exact way in which they cause the loss of control over cell division and the combinations of mutations that cause the beginning of the cancer process, is still very lacking.

It's in our gardens

About seven years ago, a project known as "The Cancer Genome Atlas" was launched in the United States (and it is no coincidence that the initials of the project in English are TCGA - the four "letters" of DNA). The project began as an experimental pilot with three types of tumors, and a few years later was expanded to its current dimensions - a concerted effort by many research institutions to identify the genetic patterns of 20 types of cancer, based on an examination of no less than 10,000 tumors. The first findings of this project strengthen the belief that there are common lines for certain tumors, even if they develop in different tissues. For example, the researchers found a genetic connection (that is, similar mutations) between certain types of breast cancer, lung cancer and colon cancer.

The two articles published in the last few days as part of the project provide further confirmation that the genetic pattern of the cancer is probably just as important - and perhaps even more - than the location of the tumor. In an article published in the journal Nature, a team of researchers from Sloan Kettering Hospital (Sloan Kettering) in New York reports on a genetic examination of more than 370 violent endometrial tumors. They found several mutations characteristic of this tumor and a violent tumor affecting the ovaries, as well as a significant genetic similarity to a certain type of breast cancer. In the second study, which was published in the New England Journal of Medicine and was led by researchers from the University of Washington, the researchers focused on one of the most violent forms of leukemia (blood cancer), known as AML. They examined two thousand patients and identified no less than 260 mutations that have some connection to the disease, but so far have not been able to point to mutations that are common to AML and other types of cancer.

Diagnostic and preventive treatment

Locating the genetic characteristics of cancer is a Sisyphean and complex task, even in an era where geneticists have at their disposal powerful tools for processing information. However, this tool is expected to be at the forefront of the fight against cancer in the years to come. It may be surprising, but so far most of the chemotherapeutic substances available to medicine in the treatment of cancer, are substances that were discovered almost at random, not drugs that were developed for a certain disease based on understanding its mechanism. An accurate diagnosis of the mutations responsible for cancer will allow science to develop more appropriate treatments for certain types of cancer (along with much more accurate diagnostic tools).

The issue of prevention is also closely related to this. Almost all the studies today that determine that a certain substance is carcinogenic are statistical studies. That is to say - they examine (many times in retrospect) the extent of exposure of a population group to a certain substance, compare it to their medical files and check if their cancer rate is significantly higher than in the general population. Many of these studies, even if they are done in good faith and with strict adherence to statistical methods, can be problematic (a good example is the many conflicting studies on the question of the safety of cell phone use). Only when we have a deep understanding - finally - of the molecular processes underlying many cancers, will we also be able to more precisely identify the substances or factors that increase the appearance of the relevant mutations (for example, exposure to radiation, cigarette smoke or agricultural pesticides), and focus prevention efforts.

Related links:
The article on endometrial cancer in Nature
The article on AML in the New England Journal of Medicine
The small light - genetic therapy for cancer