How cancer is developed - Cancer biology

Cancer is an uncontrolled proliferation of cells within the body. This proliferation leads to the formation of a mass called a tumor. The tumor will gradually invade the organ in which it was born, altering its functioning. Cells can, moreover, escape from this mass, diffuse in the organism and lead to the formation of secondary tumors. We then speak of metastases.

What is the difference between a healthy cell and a cancer cell?

Healthy cells in the body multiply in a controlled manner: they divide when necessary and are programmed to only multiply a finite number of times. When they have divided too many times or when they show damage that cannot be repaired, they die.

Conversely, the multiplication of cancer cells is out of control. These cells can divide ad infinitum. They also have the ability to induce the formation of blood vessels which will provide them with the oxygen and nutrients necessary for their multiplication. Some of them are also capable of detaching from the tissue of which they are initially part to migrate elsewhere in the body and lead to the formation of secondary tumors (metastases).

How cancer is developed?

How does cancer start?

Cancers arise from initially healthy and functional cells which have become abnormal as a result of the accumulation of alterations in their genetic makeup (DNA). These alterations (or mutations) will lead to deregulation, or even inactivation of the systems which normally allow cell division to be controlled. The cell then becomes capable of proliferating in an anarchic manner to lead to the formation of a tumor. Healthy cells have a system to detect DNA damage and repair it. When an abnormality is detected, cell division is momentarily stopped to allow its repair. If the lesion cannot be repaired, the cell sets off a program that leads to its death. This phenomenon called “apoptosis” is likened to cell suicide.

Everything becomes complicated when DNA damage affects the regions themselves involved in these processes: if mutations appear in the genes necessary for the detection of abnormalities or for triggering the cell suicide program, the cell will continue to isolate itself. It is the first step in the transformation of a healthy cell into a cancerous cell. The accumulation of other abnormalities will then lead this cell to lose its initial function and acquire properties allowing it to give rise to a malignant tumor, capable of developing to the detriment of the surrounding healthy cells and migrating to other regions of the cell in the body.

How can cell DNA be damaged?

Exposure to different substances, natural or artificial, called mutagens, can lead to the appearance of lesions in the DNA of our cells. These can be industrial chemicals or chemicals such as those found in tobacco smoke, alcohol, ionizing radiation (radioactivity) or solar radiation (UV), viruses (papillomavirus) or bacteria.

Cell dysfunction:

Checkpoints are programmed between each phase of the cell cycle, in order to verify that the current process is proceeding normally. This is an opportunity for the cell to identify the occurrence of possible abnormalities in its cell cycle and to trigger either an action to correct these errors or its self-destruction (apoptosis).

If these errors are not fixed, they accumulate. It is this accumulation, over the divisions, which is at the origin of cancer. It is considered that about ten mutations are needed for the phenomenon of cancerization to appear. The abnormalities that occur are genetic mutations, caused by errors during the replication - or reproduction - of DNA, and therefore genes, when the cell divides.

In the majority of cases, these mutations occur in the DNA of a somatic cell of a particular tissue, for example, in the DNA of a colon cell. Somatic cells refer to all the cells in the body that are not involved in reproduction and fertilization, in other words, all the cells in the body except eggs and sperm. For this reason, the mutation will not be passed on to the offspring. We speak of irregular form when it is these so-called somatic mutations that are involved in cancer. These sporadic forms of cancer are contrasted with the rare hereditary forms which are the subject of a later paragraph.

THE MUTATIONS

These mutations are due either to chance or to exposure to a risk factor. We say that they are acquired. The error that occurs in DNA can take different forms and lead to different types of mutations:

- These can be point mutations which cause very slight variations in the DNA and generate polymorphisms, without consequence in most cases. They say the mutation is silent. However, it should be noted that research is underway to elucidate the role of certain polymorphisms in the occurrence, for example, of bronchial cancer.

- These may be more complex point mutations leading to more serious effects.

- Finally, it may be more significant abnormalities involving entire genes such as deletions (losses) or translocations (exchanges) of chromosomes or parts of chromosome. For example, a part of a chromosome can break off and go to deposit on another. It is this type of phenomenon that is found in chronic myeloid leukemia where a translocation occurs between chromosomes 9 and 22.

MUTATED GENES LINKED TO THE ONSET OF CANCER

Three categories of genes have been identified which, once altered by mutations, can participate in the onset of the cancerization process. They are:

- "Proto-oncogenes": their role is to promote normal cell proliferation. A mutation in these genes - which then become "oncogenes" - can result in an activation of their function, which leads to an abnormal stimulation of cell proliferation.

- "Tumor suppressor" genes: On the contrary, they have the role of slowing down the normal proliferation of cells. A mutation in these genes can cause their function to be inactivated or reduced, which also results in an abnormal stimulation of cell proliferation.

- Genes that allow the cell to repair its DNA when it is damaged: the deficiency of these genes plays a key role in the appearance of cancers.

We already know more than a hundred oncogenes and tumor suppressor genes, as well as numerous DNA repair genes. Current research on some of these genes could lead to new avenues of treatment.

What about genetic predispositions to cancer?

The transformation of a healthy cell into a cancerous cell involves the accumulation of several lesions in the DNA of the cells. Some people are born with one or more lesions already present in their DNA, often passed on by their parents. These people have a greater risk than the general population of developing cancer because the transformation of their cells has already started when they are born. We are therefore talking about genetic predisposition to cancer.

What developments?

Since the 1980s, the frequency of cancer (i.e. the number of new cases diagnosed each year) has practically doubled. It is estimated that the increase in this index increased by 93% in men and 84% in women. At the same time, the risk of dying from the disease has fallen by almost 25%.

The increase in the incidence of the disease is partly explained by the evolution of our demographics. As the risk of cancer increases with age, there is a mechanical increase in the number of people potentially affected by the disease. The establishment of screening campaigns and the improvement of diagnostic techniques have also contributed to this evolution in the incidence of cancer and more cases can be detected.

The decrease in mortality associated with the disease is also linked to the progress made in the detection and diagnosis of cancers: discovered earlier and qualified in a more precise manner, cancers can be treated much more effectively than before. . Improvements in therapeutic strategies and the development of new, more effective and better tolerated treatments are obviously also at the origin of this positive development in cancer-associated mortality.

Finally, changes in behavior , in particular the decline in smoking  and excessive alcohol consumption observed in men over the past few decades have contributed to the reduction in the number of deaths caused by certain cancers ( lung cancer , cancer of the breast, head and neck). In women, the opposite trend is observed: the increase in smoking has led to an increase in the incidence and mortality from lung cancer.

Mechanism of Cancer

Different stages have been identified in the development of cancer: initiation, promotion and progression. First, a major lesion occurs in the DNA of a cell; the result is a transformation of this cell. Secondly, the transformed cell develops and proliferates, forming a group of identical transformed cells. Finally, in a third step, the cell acquires the characteristics of a cancerous cell: it multiplies in an anarchic manner, partly losing its differentiated character (its identity linked to the tissue to which it belonged).

The evolution first occurs locally, and then can spread via the blood and lymph to other places in the body where metastases form.

THE CHARACTERISTICS OF THE CANCER CELL

This transformation of the normal cell into a cancerous cell is a long process, which can last for decades. At the end of this transformation, the cancer cell has acquired a number of characteristics:

- its independence from the signals that usually regulate (promote or slow down) its growth and division,

- its ability to escape the process of programmed cell death,

- Its ability to divide indefinitely.

How does a tumor develop?

Cancer cells are "abnormal" cells engaged in an anarchic process where they accumulate abnormalities.

From cancer cell to tumor

The uncontrolled proliferation of cancer cells will result in the formation of a malignant tumor.

- As soon as the tumor reaches 1 or 2 millimeter (s), the cancer cells trigger angiogenesis, i.e. the formation of new blood vessels which irrigate and supply the tumor. Without this blood supply, the tumor could not continue to grow.

- Cancer cells seep into nearby healthy tissue and escape from their place of origin to develop secondary tumors (metastases) in other organs.

- Cancer cells “hijack” the cells around them for their own benefit and use them to their advantage. A tumor is always formed by an agglomeration of cancer cells and normal cells that work together. 

Successive stages of cancer development

In the absence of treatment, the majority of "solid" tumors (cancers) evolve by always following the same stages, but at very variable speeds and according to methods specific to each type of cancer:

- Stage 1: The disease begins with a precancerous lesion that contains cells in the process of transformation. Not all precancerous lesions necessarily lead to cancer.

- Stage 2: A cancer cell appears and begins to multiply. At first, the small tumor remains localized in the original tissue.

- Stage 3: The tumor grows and begins to invade neighboring tissues. The metastases appear. Often, they first affect the lymph nodes. The metastases then spread to other organs and are responsible for most cancer deaths.

There are different stages (degrees of extension) of cancer.

- Stage 1: The tumor is single and small.

- Stage 2: the tumor is larger.

- Stage 3: The tumor invades the lymph nodes or surrounding tissue.

- Stage 4: presence of metastases in other organs distant from the original tumor.

How to analyze the development of cancer cells:

Tumor markers and medical imaging are central to the diagnosis. If suggestive symptoms or when a screening test has given a positive result, various examinations must be carried out to confirm or deny a diagnosis of cancer. If the diagnosis is confirmed, these examinations will also make it possible to specify the nature of the tumor, to know its degree of evolution and to detect the possible presence of metastases at a distance from the primary tumor. All of these elements are essential for the implementation of an appropriate treatment. Any diagnosis of cancer begins with a careful physical examination, most often followed by the ordering of a blood test and medical imaging tests. Blood tests ordered as part of a cancer diagnosis may include testing for tumor markers.

Tumor markers are molecules produced in excess by cancer cells. Some normal cells in the body can also synthesize these molecules, but in small quantities. Thus, when the concentration of a tumor marker rises in the blood or urine of a patient, it may correspond to the presence of a tumor in their body. However, the increase in the concentration of a tumor marker is not sufficient to establish a diagnosis: other pathologies, benign or malignant, can lead to the same effect. Likewise, a normal dosage of tumor markers is not sufficient to exclude a diagnosis of cancer. 

Author: Vicki Lezama