Why are tumors deadly

Cancer is usually malignant tumors, i.e. new tissue formations (neoplasias), which can cause death by growing into organs or changing organ functions and the spread of secondary tumors (metastases) throughout the body. In principle, any organ in the body can be affected, and depending on the origin of the tissue, a distinction is made between malignant (malignant) epithelial carcinomas - the most common types of cancer such as cancer of the breast, prostate, lung, pancreas and liver - and less common malignant mesenchymal tumors (sarcomas) . Malignant tumors of the blood cells are often referred to as "blood cancers" and experts classify them into special leukemias, lymphomas and others. Cancer is therefore a disease in which body cells multiply in an uncontrolled manner and displace and destroy healthy tissue.

Yeast, fly, human

Life in every form is determined by the genetic material and its implementation. So there are also fixed genetic programs in our genetic material that regulate the growth and division of cells. Their strict control is best seen in the development of a fertilized egg cell into a fully grown organism. The multiplication of cells through cell division (proliferation) goes hand in hand with their specialization, i.e. the exercise of certain functions, cell differentiation. Genetic programs ensure that cells in a certain place divide and differentiate in their function in such a way that a functional organ is created: for example, epithelial cells of the intestine for food intake, liver cells for metabolic functions or nerve cells for stimulus conduction.

It is fascinating to see that the regulatory circuits and mechanisms that control cell division are very similar - from brewer's yeast to roundworms and fruit flies to mice and humans. In addition to the formation of new cells, we must also speak of cell death. Cells that are no longer needed because they are too old or can no longer perform their natural function are eliminated by what is known as programmed cell death (apoptosis), another genetic program recorded in our genetic material. The cells break down themselves and are taken in by scavenger cells or neighboring cells that patrol the body. Programmed cell death is therefore a natural thing that takes place continuously in our body, for example when replacing old skin, intestinal or blood cells.

The processes of cell division and death are carried out by highly complex regulatory mechanisms. The actual controls exercise genes which, on the one hand, stimulate cell division (growth or proto-oncogenes) or, on the other hand, inhibit cell division (tumor suppressor genes). There are also genes that inhibit programmed cell death, i.e. growth genes, and genes that stimulate cell death, i.e. tumor suppressor genes. If a cell is now stimulated to divide by a growth signal, the combination of the activity of the growth and tumor suppressor genes will control cell division and cell death in such a way that with a strong growth signal the cell will enter the cell cycle and divide without cells die. The resulting daughter cells can continue to divide by themselves or, through differentiation, take over their final organ function.

If all these genes and control circuits function properly, the tissues and organs develop in the intended size and with the expected function. If a proto-oncogene, which normally converts growth signals into cell division, is now activated in a cell without a growth signal, cells are stimulated to divide at the wrong time in the wrong place. This can be caused by activating mutations, duplication of the gene in the genetic material or a malregulation of the use of the gene. This turns a normal growth gene (proto-oncogene) into a cancer gene (oncogene). The same effect naturally arises from the loss of tumor suppressors: Here, gene function is impaired by an inactivating mutation, the loss of a piece of chromosome or a lack of activation of the tumor suppressor gene.

Uncontrolled cell reproduction can also occur due to defects in the regulation of cell death: If the function of genes that initiate cell death is missing or there is too much function of genes that prevent cell death, too many cells are formed. Indeed, most cancers have a combination of all of these genetic changes. Changes in gene function through mutations or other damage in the genetic material mean a genetic cause of cancer. The number and type of mutations in onco and tumor suppressor genes differ between different types of cancer. There are certain forms of leukemia in which only one genetic event, the activation of an oncogene, causes the cancer. Colon cancer, on the other hand, appears to have up to seven genetic changes. Even within one type of cancer, a wide variety of defects can be found in the genetic programs. For example, breast cancer can be differentiated into at least five different types based on the genetic changes.

Old age disease

Cancer is also a disease of aging. Normally, damage to the genetic material caused by errors in the duplication during cell division or by metabolic influences or environmental factors are repaired immediately. Unfortunately, however, the damage to the genetic material increases with age, while the repair mechanisms in the body work less effectively. With aging, this inevitably means that body cells can evade growth control and the incidence of cancer diseases will continue to increase with the average age of the population.

This also gives an answer to the question of whether cancer has always existed or is an "invention" of the modern age: Even the ancient Egyptians used hieroglyphics for breast cancer, but at that time people first had to get old enough to experience cancer. Another question is why there are children and young people with cancer. Such cancers are often caused by defective embryonic development programs. Cancer can also be inherited: a mutation in a tumor suppressor gene can be passed on from one parent, whereupon the offspring is very likely to develop cancer at a relatively young age. There are families in which some female members carry a mutation in the BRCA-1 tumor suppressor gene and develop breast cancer at an early age. Further examples are defects in the p53 tumor suppressor gene or in other genes that are responsible for repairing the genetic material. Defects in the genetic material, for example caused by UV radiation from the sun, can no longer be adequately repaired in these patients, which leads to skin cancer and other types of cancer.

There are also individual differences in the gene structure (polymorphisms) in the genetic material of humans that do not amount to a mutation. Certain constellations of this make an individual more or less susceptible to cancer. Everyone knows the famous grandfather who turned 90 despite heavy smoking (although it has been proven that the majority of smokers massively shorten their lives). So we live with genetic make-up that makes us susceptible to cancer in different ways. There are other causes of cancer as well. Certain forms are caused by viral infections, such as untreated hepatitis B virus infection, which can lead to liver cancer, or human papillomavirus (HPV), which causes cervical cancer, a discovery that is relatively quick to clinical application, namely the HPV vaccination in young girls.

The carcinogenic effect of tobacco no longer needs any special explanation. Unfortunately, there are plenty of other environmental toxins that damage genetic material: Dioxins and polychlorinated biphenyls (PCBs) can still be found in hydraulic fluids, coolants and plastic softeners. Unfortunately, we are also confronted with carcinogenic substances through our diet: for example through the genetically damaging poison aflatoxin in mold-infested peanuts and through the benzopyrene in charred grilled meat.

Multi-stage creation

So far, we have only talked about the first, but perhaps the most important, step in the development of cancer: from normal tissue to the first “preneoplastic lesions”, i.e. clusters of cells that divide in an uncontrolled manner. However, the formation of fast-growing, malignant tumors that form metastases requires further steps: the formation of new blood vessels to supply the growing tumor with oxygen and nutrients ("tumor angiogenesis") as well as the transition from benign tumor to malignant cancer, its cells in the surrounding tissue can grow in and finally spread through penetration into the lymphatic or blood vessel system in order to form daughter tumors ("metastases") in distant organs.