The Origin of Cancer

When and how does Cancer originate?

I have written in quotes "Cancer", because first I must establish that there are hundreds of types of cancer, each of them with a different cause and genetic information and therefore with different evolution, prognosis and treatments. However, throughout the count through which we are going to travel we will refer to "cancer." 

Of course, there is still no answer to this question, a situation that has led many scientists and researchers throughout history to pose potential hypotheses, some of which have achieved answers and others that are still the subject of intense clinical research. laboratory at the genetic and molecular level.

Cancer, according to the evidence obtained so far, goes hand in hand with the history of humanity. In prehistoric times it was believed to be caused by diabolical spirits, natural forces or according to Hebrew, Greek and Roman beliefs: by sin, violation of divine rules or the Wrath of God. The oldest evidence of a case of cancer was published in (Odes et al), is an Osteosarcoma in the metatarsus of a Hominin found in the Swartkrans Caves in South Africa and it is estimated that this evidence dates back approximately 1.7 million years.

There are also descriptions of tumors in the Edwin Smith papyrus, from ancient Egypt; written approximately in the year 1,600 BC; which date back to approximately 3,000 years BC. The text also describes potential treatments for these tumors with cautery.

The term "cancer", derived from Greek karkinos or crab, is attributed to Hippocrates of Kos (460 – 370 BC), considered the father of medicine. The Hippocratic schoolCorpus Hippocraticum) described the disease as the imbalance between the four "Humors" (Blood, Phlegm, Yellow Bile and Black Bile). Later, Claudius Galen Nicon of Pergamon, Better known as Galen (129 AD – 215 AD), he considered that cancer was caused by an excess of black bile.

Galen is also credited with incorporating the word "Onkos", used to describe a mass, tumor or swelling. The contributions of Hippocrates and Galen to medicine dominated medical knowledge for a little more than 14 centuries. It seems that, under the concept of humoral theory, cancer was able to go almost unnoticed during the period of scientific and cultural lethargy of the Middle Ages.

Despite some contributions to the treatment of breast tumors mainly, the concept that prevailed since Hippocrates was to "not touch" cancer because it was considered incurable and very little progress was made in finding the potential cause of the disease. At the beginning of the Modern Age, the first to question and oppose the humoral theory was the Swiss doctor, alchemist and astrologer Theophrastus Phillippus Aureolus Bombastus von Hohenheim known as Paracelsus (1493 – 1541), who postulated that cancer was caused by the accumulation of "toxic" substances in the blood and pointed out some elements such as: salt, sulfur and arsenic, mainly in mining workers, metallurgists and chemists. It was the first association between cancer and chemicals.

Bernardino Razzini (1633 – 1714), Italian doctor considered the father of occupational medicine, described in the second edition of his book From Morbis Artificum Diatribe published in 1713, the high incidence of breast cancer in nuns, as well as the low incidence of cervical cancer in this population; He concluded that the latter was due to sexual abstinence and the former to poor hormonal development. Today there is evidence of the protective effect of early pregnancies, mainly under 25 years of age, and some types of breast cancer. Subsequently Percivall Pott (1714-1788), English surgeon publishes the association between scrotal cancer and exposure of the scrotal skin to chimney soot in young chimney sweeps in London and recommends the use of protective clothing to prevent cancer in these young people .

With the performance of autopsies and the relationship of symptoms and signs of diseases with pathological findings at the beginning of the Modern Age, parallel to the development of microscopy, knowledge of diseases in general deepened and other possible causes of the disease began to be postulated. cancer.

Robert Hook (1635 – 1703) English scientist, in his book Micrograph published in 1665, identifies and uses the term "cell" for the first time. Subsequently, François Vincent Raspail (1794 – 1878), French doctor, chemist and politician, coined the phrase: "omnis cellula e cellula"(Every cell comes from another cell), from which Rudolf Virchow (1821-1902), German scientist and researcher, popularized the second principle of cell theory, thus laying the scientific foundations for the future understanding of cancer. Furthermore, he coined the term "neoplasia" for the uncontrolled growth of pathological cells.

In the following years, great contributions were made to theories about the origin of cancer, Theodor Heinrich Boveri ( 1862 - 1915) German embryologist and geneticist, postulated at the beginning of the 20th century that cancer could be caused by altered chromosomes in a cell that lead to uncontrolled cell division.

Wilhelm Ludvig Johannsen ( 1857 - 1927), was a botanical, geneticist and physiologist Danish who in 1909 coined the term "gene" instead of "hereditary factor." In 1953 James D Watson y Francis Crick describe the DNA structure and in the following years the genetic code, which, put simply; It is the set of rules that defines how a sequence of nucleotides in RNA is translated into a sequence of amino acids in a specific protein.

This development of genetics has had an important impact on the understanding of the causes of cancer, which has allowed us to establish that cancer can occur from errors (mutations) in the replication of genetic material, which are transferred via cell division to new generations of cells. Thus cancer goes from being a disease of the cells to a disease of the genes.

Inside each cell of our body, there are genes known as proto-oncogenes which play an important role in the control of cell division and genes whose products prevent cell division or lead to cell death (apoptosis) directly or indirectly (tumor suppressor genes). If a proto-oncogene suffers a mutation, it can be activated and produce uncontrolled cell division, contributing to the development of cancer.

Once a proto-oncogene is activated by a mutation caused by one or more of the external (exogenous) or internal (endogenous) factors, it is demonized. oncogene. The activation of an oncogene occurs when undergoing structural alterations such as: chromosome rearrangements, gene fusion, gene amplification or point mutations (substitutions).

The development of a malignant tumor requires complex interactions between multiple factors, both Exogenous (environmental = chemicals, radiation, viruses, etc.) and Endogenous (genetic, hormonal, etc.), which produce multiple somatic mutations which contribute to the transformation process. neoplastic and carcinogenesis. One of the questions that has prevailed over the years is knowing how many mutations are necessary for the transformation of a normal cell into a malignant cell.

At first it was postulated that "few" mutations were required (6 to 8 mutations), but with the advancement of knowledge at the molecular level, it has been observed that the number of mutations necessary for carcinogenesis is highly variable in cells from different countries. fabrics. The exact number of mutations required is still unknown, as is the sequence of these mutations; For example, it has been observed that in some tumors mutations that occur early may be late alterations in other tumors.

Other factors that intervene in the variability of these mutations are: the microenvironment of each cell, alterations in different chromosomes, alteration in the nucleotide sequence in DNA, failure in DNA damage repair mechanisms. Furthermore, it is not a simple combination of mutations for all tumors, but rather different combinations in each of the tumors and consequences of different mutations in each case.

Other important aspects should also be noted because the carcinogenesis process frequently occurs through multiple steps or stages (initiation, promotion and progression); and this can occur throughout the life of an individual in some cases and in a relatively short period in others.

In 2000 Douglas Hanahan y Robert Weinberg published "The Hallmarks of Cancer", which describes six essential characteristics in the transformation of a normal cell into a neoplastic cell: Self-sufficiency in growth signals, Resistance to growth inhibition, Evasion of apoptosis, unlimited potential for replication, Sustained angiogenesis and activation of invasion and metastasis. In 2011, the same authors described two additional characteristics: Tumor-promoting inflammation and genomic instability and mutation.

Although these "hallmarks" or essential characters in the evolution of cancer have been the pillar of many advances both in deciphering the process of carcinogenesis and in the development of new treatment strategies, the complexity of cancer pathogenesis has not yet been elucidated. That is, knowing the precise molecular and cellular mechanism that allows the initiation and evolution of a preneoplastic cell to an aberrant cell that finally progresses to a malignant neoplasm.

In the most recent publication by Douglas Hanahan, in January 2022, (17) new characteristics continue to be described that enable the complex processes of cellular transformation towards a malignant neoplasm; The near future will give us more information about it.

REFERENCES

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