What kind of disease is cancer?

Mechanism of disease development

Atlas company blog, Geektimes

Everyone has heard about cancer one way or another. Someone has seen messages on social networks, someone has helped relatives and friends to survive this disease, and someone has come face to face with it. 

In any case, cancer scares. Most of the fears are born due to misconceptions about the disease or simply ignorance. We at Atlas believe that knowledge is power, so we have prepared a series of articles where we will tell you about cancer: how it forms, whether it can be prevented, and how to build the treatment process.

Today we tell you what cancer is, how it develops and why it is so difficult to defeat.

Before we talk about the mechanism of tumor formation, let's understand a little terminology and remember how healthy cells and tissues of the body are renewed.

Why is cancer so called

What patients call cancer, in the language of medicine, means an oncological disease or a malignant tumor. A tumor, neoplasia or neoplasm is a cluster of atypical cells that divide uncontrollably and refuse to die.

The ancient Greek physician and philosopher Hippocrates was one of the first to describe malignant neoplasms. In his writings, he gave them the name karkinos, which means "cancer" in Greek: in the section, large tumors reminded him of cancers. Later, the ancient Roman physician Cornelius Celsus translated the term into Latin – this is how the modern name cancer appeared. Another Roman physician and surgeon Claudius Galen described benign tumors with the word oncos. Today, oncology is a science that studies the mechanism of formation of benign and malignant tumors, methods of their prevention and principles of treatment.

The English-language name of all malignant neoplasms cancer in Russian translates as "cancer". In this sense, the term can be used in everyday life, but doctors call "cancer" only carcinoma – a malignant tumor of epithelial tissue that lines the surface of the body, mucous membranes and cavities of internal organs, and also forms most of the glands.

In addition to carcinoma, malignant tumors include sarcoma, melanoma, leukemia and lymphoma. Sarcoma is a malignant tumor of connective tissue. Connective tissue includes muscles, ligaments, cartilage, joints, bones, tendons, and deep layers of skin. Melanoma is a malignant tumor of melanocytes (skin cells). Leukemia or leukemia is a malignant neoplasm of hematopoietic tissue, and lymphoma is lymphatic.

How healthy cells and tissues are renewed

All human organs and tissues are made up of cells. They have the same DNA, but take different forms and perform different functions. Some cells are at war with bacteria, the second carry nutrients, the third protect us from the effects of the external environment, others consist of organs and tissues. At the same time, almost all cells are renewed so that the human body grows, functions and recovers from damage.

Cell renewal is regulated by growth factors. These are proteins that connect to receptors on the cell membrane and stimulate the process of division. When a new cell separates from its parent, a cascade of reactions is triggered in it, and it receives specialization – differentiates. After differentiation, only those genes that determine its shape and purpose are active in the cell. We can say that now the cell has a personal instruction on what to do and how to do it.

All fabrics are updated at different rates. The cells of the central nervous system and the lens of the eye do not divide at all, and the epithelial cells of the small intestine completely change every 4-5 days. Tissues that are constantly being updated contain a layer of stem cells. These cells have no specialization, but can only divide and create either their own copy without specialization, or a differentiated cell of the tissue in which they are located.

New cells replace the damaged old ones. The damaged cell "understands" that it will no longer benefit the body, and launches a death program – apoptosis: the cell commits voluntary suicide and gives way to a healthy one. 

How a cell becomes malignant

During division or due to exposure to DNA-damaging compounds, approximately 10,000 errors occur in the cell genome per day. But our body is able to cope with them. Special enzymes repair breakdowns or launch an apoptosis program. If the change remains without repair, the mutation remains in the DNA chain.

A mutation is a change in DNA that is transmitted to other cells. Mutations can be hereditary and somatic. Hereditary mutations occur only in germ cells and are passed on to the next generation. 

Mutations occur much more often in other cells. Somatic mutations occur independently of each other in different cells of the body and are not inherited. Some factors significantly increase the frequency of somatic mutations. Cigarette smoke, ultraviolet light, radiation and retroviruses are powerful mutagens that can lead to mutations in DNA. 

When a cell with a mutation divides, the defective DNA doubles and is transferred to a new cell. If another mutation occurs in it, it is added to the existing one. Thus, somatic mutations accumulate in different cells of the body throughout life. This explains human aging and the formation of malignant tumors. By the way, they are closely related: with age, the risk of developing a malignant tumor increases.

Statistics of the P.A. Herzen MNIOI.

What mutations lead to cancer

Imagine that several mutations happened in one cell. The first affected the genes that are responsible for division, and the second disrupted the mechanism of triggering apoptosis. If these two mutations meet, then we will get a cell that constantly divides and refuses to die.

Tumor suppressor genes and proto-oncogenes are genes that regulate division, differentiation and apoptosis. A healthy cell uses these genes to determine what it will become, what functions to perform and when to die. When these genes are damaged, the cell does not have access to instructions, and it becomes unmanageable.

Today, about 40 proto-oncogenes are known, and 14 of them are associated with a high risk of tumor development. As an example, ERBB2 (HER-2) is often mutated in breast cancer, KRAS – in pancreatic and colon cancer, BRAF – in melanoma. 

The most well–known tumor suppression gene is BRCA1. Mutations of this gene increase the risk of developing breast cancer and ovarian cancer. Another well-known suppressor gene is TP53: mutations in it are detected in half of cancer cases.

How a malignant tumor develops

Immortal cells continue to divide – and the tumor grows. The accumulation of cells develops into dysplasia – an atypical neoplasm for the tissue. A non-invasive tumor or cancer in situ means that the neoplasm has not yet sprouted through the thin border between epithelial and connective tissue (basement membrane). This stage is characterized by equilibrium, which we will discuss in more detail later. Violation of the basement membrane is the first sign of a malignant process.

nccs.com

A malignant tumor cannot grow further until it gets access to nutrients. Therefore, tumor cells secrete various growth factors, but the most important of them is vascular endothelial growth factor (VEGF). It stimulates the formation of a network of capillaries through which cells gain access to nutrients. Now the tumor can grow into the surrounding tissues and destroy them. 

DNA damage continues to occur in a malignant cell, but it does not recover. The cell spends all its resources on infinite division. Due to constant mutations, cells with a variety of shapes and properties appear in the tumor.

The body is trying to fight the tumor, and the environmental conditions for malignant cells are constantly changing. Only those malignant cells that can resist change survive and divide further. We can say that natural selection takes place among the cells of a malignant tumor.

As the tumor divides, tumor stem cells appear in the neoplasm. They can copy themselves and produce ordinary malignant neoplasm cells. Tumor stem cells are difficult to destroy during treatment, which leads to relapses.

Over time, as a result of selection, a cell appears capable of detaching itself from the tumor, finding a suitable place for a secondary focus to begin dividing in a new environment. This is how metastasis is formed. 

Not all tumors are made up of malignant cells. Benign cells differ in that they partially or completely retain their specialization. They divide slowly, copy DNA exactly and remain similar to the cells of the original tissue. DNA repair continues to work in a benign tumor, there are not so many mutations and natural selection, so such a tumor is easily amenable to surgical treatment. But due to additional mutations, cells of benign formations can turn into malignant ones. For example, due to exposure to ultraviolet radiation, moles can degenerate into melanoma (a malignant neoplasm of the skin).

Why the immune system can't cope with a malignant tumor

Another feature of malignant tumors is the reaction of the immune system to them. There are three stages of the immune system response:

Elimination. Damaged cells express tumor antigens on their surface, to which the main guardians of the immune system – macrophages and lymphocytes - react. They find and destroy the enemy. At this stage, the tumor cannot grow into the surrounding tissues, therefore it is called a non-invasive or in situ tumor (in situ).

Balance. Some cells begin to disguise themselves – synthesize fewer antigens. The immune system cannot find and destroy them, but recognizes the remaining malignant cells. In the equilibrium stage, the immune system cannot cope with the tumor completely, but limits its growth. This condition can last for years and not manifest itself in any way.

Impotence. Due to genetic instability, cells with different mutations are constantly being born in the tumor. Therefore, sooner or later, immunosuppressive cells appear, which reflect the attack of the cells of the immune system and suppress the immune system.

How does metastasis appear

The secondary growth site of a malignant tumor is called metastasis. Metastasis is a superpower of a malignant tumor, a complex process for which the tumor has been preparing for a long time. 

First, malignant cells secrete special vesicles – exosomes. They travel throughout the body, find tissue suitable for metastasis and prepare it for the arrival of cancer cells. So an attractive niche is formed in normal tissue, where malignant cells can settle and begin to divide. Sometimes cancer cells resemble self-learning artificial intelligence, but this is not the case.

Also, some cells are able to secrete special signaling molecules that reprogram macrophages. Some of them stop fighting and begin to perceive the tumor as damaged tissue. Such macrophages secrete various growth factors that help tumor cells divide. At this stage, immune cells are divided into two opposite camps: some continue to destroy the tumor, while others help it grow. This is a turning point, after which the tumor begins to grow and metastasize.

A malignant cell cannot simply detach itself from the tumor and begin to travel through the body. It must be able to detach from other cells, penetrate into the depths of the surrounding tissues, survive after entering the blood and lymphatic vessels. To do this, malignant cells secrete special substances that allow them to move, destroy cells of other tissues and hide from the immune system.

Together with the lymph, malignant cells enter the lymph nodes. The lymphocytes in them are trying to stop and destroy the enemy so that he does not pass on. Due to the inflammatory process, lymph nodes increase, and most cancer cells die. The surviving cells can settle in the lymph node tissue and metastasize. As a rule, the cells of a malignant tumor first affect the nearest lymph nodes and only then get to the distant ones. 

Malignant cells continue to search for prepared tissue as they move through the body. Most of them die in an unusual environment, so the search can take a long time. But sooner or later, a cell appears capable of leaving a blood or lymphatic vessel, attaching itself to the prepared tissue and starting to divide in a new place. This is how a secondary focus, or metastasis, is formed.

Schematic image of a malignant tumor cell that can metastasize (Researchgate.net ).

Different types of malignant tumors have favorite places for metastasis. For example, breast cancer often metastasizes to the lungs, liver, bones and brain. The name of the disease is always associated with the primary tumor and does not depend on the places of metastasis.

What does stage four cancer mean and why is it the most dangerous

For diagnosis, it is extremely important to assess the type, degree of prevalence, differentiation and growth rate of a malignant tumor. There is an international classification of TNM for this.

T – tumor (tumor). Next to the letter T can be a number from 0 to 4, which characterizes the prevalence of the primary tumor. T0 – the tumor cannot be determined. The higher the number, the larger the size of the tumor and the likelihood of germination into the surrounding tissue. Tis is a designation for a non–invasive tumor.

N – nodes (nodes). From 0 to 3. Indicates the absence, presence or degree of prevalence of metastases in regional lymph nodes. If metastasis has appeared in a distant lymph node, it belongs to criterion M.

M – metastases (metastases). Distant metastases either exist – M1, or they do not exist – M0.

If one of the components of the system cannot be measured, then the symbol X is placed next to the letter.

Epomedicine.com

Classification of TNM allows you to determine the stage of the tumor process.

The first stage is a small tumor at the site of occurrence. The second stage is an enlarged tumor that has sprouted into the surrounding tissues and may have metastasized to the nearest lymph nodes. The third stage is a rather large tumor that has metastasized to the nearest lymph nodes. The fourth stage is a tumor with metastases in other organs and tissues.

As a rule, it is impossible to completely cure a tumor at the fourth stage: drug therapy can only slow down the course of the disease. Such patients are provided with palliative care, its task is to improve the quality of life of the patient.

How to fight cancer

A malignant tumor seems to be a monster that uses all the forces and functions of the body for its own good. But do not forget that the appearance of this monster can be prevented if you know about your risks and preventive measures. 

In addition to prevention, it is important to undergo regular examinations to diagnose a malignant neoplasm at an early stage. While the tumor has not had time to spread to other tissues and organs, it is treatable. 

In the next article Atlas will tell you in detail how to reduce the risks of developing malignant neoplasms, as well as give instructions on when and what examinations to undergo in order to protect yourself.

In the meantime, we offer to take the test from Cancer Prevention Foundation. Based on its results, it is possible to roughly assess the risks of developing malignant tumors.

Portal "Eternal youth" http://vechnayamolodost.ru 15.06.2017